• 2020) provide an initial framework for understanding the underlying mechanisms by integrating enhancer and transcriptional alterations that occur during the progression of basal cell and squamous cell carcinomas. (nih.gov)
  • ChIP-seq identifies Sox17 -bound enhancers and direct transcriptional targets. (xenbase.org)
  • Together, these signaling and transcriptional pathways set up complex and only partially defined regulatory networks that result in the progressive delineation and specification of heart progenitors. (biologists.com)
  • Transcriptional control is likely a key feature of regeneration competency as thousands of genes change in expression. (osuchildrensmusclegroup.org)
  • Furthermore, despite the failure to gain active histone marks at thousands of enhancers, transcriptional activation of nearby genes is largely unaffected, thus uncoupling the regulation of these chromatin events from transcriptional changes during this transition. (biomedcentral.com)
  • Therefore, the naive to formative transition provides an ideal model to study relationships in enhancer mechanics and transcriptional regulation. (biomedcentral.com)
  • Modern epigenomic techniques are powerful tools to dissect complex regulatory networks, providing the ability to systematically analyse chromatin landscape and on-going transcriptional programs. (ox.ac.uk)
  • Using an EdnrB enhancer, we generated a comprehensive temporal map of the chromatin and transcriptional landscape of VNC in the avian model, revealing three VNC cell clusters (neural, neurogenic and mesenchymal), each predetermined epigenetically prior to neural tube delamination. (ox.ac.uk)
  • Among the identified transcriptional regulators inactivated in lung adenocarcinoma vs . normal lung, NKX2-1 was linked to a large number of silenced enhancers. (prolekarniky.cz)
  • Among the activated transcriptional regulators identified, CENPA, FOXM1, and MYBL2 were linked to numerous cancer-specific enhancers. (prolekarniky.cz)
  • Identification and characterization of key transcriptional regulators and associated enhancers in lung adenocarcinoma provides important insights into the deregulation of lung adenocarcinoma epigenomes, highlighting novel potential targets for clinical intervention. (prolekarniky.cz)
  • We model transcriptional gene regulation by using a hybrid approach and applying it to the well characterized segmentation gene regulatory networks in Drosophila development. (ecmiindmath.org)
  • It is important to understand at this level how a specific molecular configuration of the regulatory sequence gets formed and, being formed, how it influences the basal transcriptional machinery initiating transcription. (ecmiindmath.org)
  • Three chromatin states were associated with regulatory regions known as promoters, which sit close to genes and allow them to be read. (nih.gov)
  • Promoters active in both cells types were associated with general metabolism genes. (nih.gov)
  • Promoters, enhancers and physical interactions between regions of DNA are important in ways that are only now becoming apparent, directing phases of development, and often perturbed in cancers. (birmingham.ac.uk)
  • In a Novartis-sponsored study in the New England Journal of Medicine, researchers found that a CRISPR-Cas9-based treatment targeting promoters of genes encoding fetal hemoglobin could reduce disease symptoms. (genomeweb.com)
  • Nucleosome reorganization may be a critical feature of normally dormant cis-regulatory elements and promoters. (osuchildrensmusclegroup.org)
  • The analysis of both authentic Dorsal target genes and defined synthetic promoters suggests that the ectopic gradient is sufficient to generate the full repertory of DV patterning responses along the AP axis of the embryo. (sdbonline.org)
  • This project focuses on developing computational tools for better analysis of the wealth of data from chromosome conformation capture assays with the ultimate goal of inferring functional chromatin contacts such as those between enhancers and promoters. (ucsd.edu)
  • Epigenomic profiling of histone modifications allows genome-wide chromatin signature mapping and classification of sites of regulatory activity (e.g. distal elements/enhancers, promoters, repressed regions, etc. (ox.ac.uk)
  • The vast majority of these, however, lie outside of known genes, as 98.5% of our genome doesn't code for proteins. (nih.gov)
  • To gain insights into these non-coding regions, a team of scientists partly supported by NIH's National Human Genome Research Institute (NHGRI) carried out a genome-wide survey of epigenetic marks - factors that change the way genes are read, or expressed, without changing the DNA sequence itself. (nih.gov)
  • They found very large differences in regulatory elements, which are part of the non-coding regions of the genome. (embl.org)
  • "Identifying All of Cancer's Manifestations through Integrated Pan Cancer Analysis" Dr. Josh Stuart presented the recent work of The Pan-Cancer Initiative of The Cancer Genome Atlas (TCGA) Research Network, including the analysis of thousands of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels in order to uncover data-driven tumor subtypes. (biomedcentral.com)
  • While each DNA blueprint, or gene, encodes for a different machine or structure, the genome, the collection of DNA wrapped up inside the nucleus, is much more active than a quiet library of neatly stacked blue-prints. (birmingham.ac.uk)
  • We are investigating the impact of specific classes of gene mutations, such as ATM, BRCA1, and MYBL2 on genome integrity. (birmingham.ac.uk)
  • The Human Genome Project (HGP) was the international, collaborative research program whose goal was the complete mapping and understanding of all the genes of human beings. (umassmed.edu)
  • Genome wide association studies (GWAS) have identified mutations in non-coding regulatory regions as the most common features associated with human disease. (umassmed.edu)
  • In contrast, genome-wide comparative studies of steady-state systems showed that only a small fraction of active enhancers are conserved. (umassmed.edu)
  • To identify new risk genes, we utilized an international consortium of 4241 PAH cases with exome or genome sequencing data from the National Biological Sample and Data Repository for PAH, Columbia University Irving Medical Center, and the UK NIHR BioResource - Rare Diseases Study. (biomedcentral.com)
  • Genetic analyses of larger cohorts using gene panels, exome sequencing (ES), or genome sequencing (GS) have further defined the frequency of individuals with deleterious variants in PAH risk genes and have identified novel candidate risk genes. (biomedcentral.com)
  • They also explored potential passenger mutation interactions with transcription factor binding sites and other regulatory features in the genome and looked at the relationship between proposed passenger mutations and tumor features overall - from the apparent mutational processes at play to the mutation patterns in tumor sub-clones. (genomeweb.com)
  • Enhancer Predictions and Genome-Wide Regulatory Circuits. (beerlab.org)
  • Abstract Precise control of developmental processes is encoded in the genome in the form of gene regulatory networks (GRNs). (ox.ac.uk)
  • By coupling NC-specific epigenomic and single-cell transcriptome profiling with genome/epigenome engineering in vivo , we identify multiple regulatory layers governing NC ontogeny, including NC-specific enhancers and super-enhancers, novel trans -factors and cis -signatures. (ox.ac.uk)
  • We develop methods that are based in statistics, machine learning, optimization and graph theory to understand how changes in the 3D genome affect cellular outcome such as development, differentiation and gene expression. (ucsd.edu)
  • Understanding how these programs, encoded at the genome level, are translated into intricate networks of interacting biological components (genes, proteins, RNA) is essential to our understanding of mechanisms underlying developmental processes and human diseases, triggered when biological circuits go awry. (ox.ac.uk)
  • My project, PATTERNS, aims at studying the polygenic selection targeting the regulatory regions of the genome and will be done in collaboration with Frédéric Austerlitz (Musée de l'Homme, Paris). (inrae.fr)
  • 1 It turns out that the bacterial genome has a few high-level instructions that control a few middle-level processes, that in turn control a massive number of protein-coding genes. (creation.com)
  • Comprehensive molecular profiling of lung adenocarcinoma: The cancer genome atlas research network. (prolekarniky.cz)
  • 100.000 cCREs in total), dispersed within the genome and present in cis-regulatory regions of ~81% of human genes, as calculated following gene enrichment analysis. (mdpi.com)
  • Remarkable progress in science and technology has led to the development of powerful tools for genome sequencing and editing increasing ability to study gene expression and function at multiple levels from cells to populations. (cdc.gov)
  • Aerts completed his postdoc training working on the genomics of gene regulation in the fruit fly model Drosophila melanogaster in the lab of Bassem Hassan at VIB in Leuven, including a research visit at the Developmental Biology Institute of Marseille, Luminy (IBDML), in France, with Denis Thierry and Carl Herrmann. (wikipedia.org)
  • Aerts teaches several courses, including Introduction to Bioinformatics, Bioinformatics: Structural and Comparative Genomics, Bioinformatics and Systems Biology: Sequence, Structure & Evolution and Bioinformatics and Systems Biology: Expression, Regulation and Networks at the University of Leuven. (wikipedia.org)
  • These are sequences of DNA that don't carry instructions for making proteins, but are responsible for other functions such as gene regulation. (embl.org)
  • Our loss- and gain-of-function studies, as well as the observed genetic interactions among Dorsocross, tinman and pannier , suggest that co-expression of these three genes in the cardiac mesoderm, which also involves cross-regulation, plays a major role in the specification of cardiac progenitors. (biologists.com)
  • Peak evaluation is complex, as gene expression regulation involves interactions between combinatorial transcription factor binding sites and chromatin states. (biomedcentral.com)
  • Dissecting gene regulation with multimodal sequencing. (costalab.org)
  • As primary determinants of gene regulation, transcription factors not normally active in uninjured CMs are likely required for triggering regeneration. (osuchildrensmusclegroup.org)
  • Target gene regulation is mediated by general chromatin regulators which are recruited to enhancers bound by TFs. (biomedcentral.com)
  • The Huang (1997) paper also clearly summarizes what is known about the regulation of genes involved in dorsal/ventral patterning. (sdbonline.org)
  • The epigenetic regulation of spatiotemporal gene expression is crucial for human development. (researchgate.net)
  • Here, we systematically delineate the acute innate immune response to endotoxin in terms of human macrophage enhancer activity and contrast with endotoxin tolerance, profiling the coding and non-coding transcriptome, chromatin accessibility and epigenetic modifications.ResultsWe describe the spectrum of enhancers under acute and tolerance conditions and the regulatory networks between these enhancers and biological processes including gene expression, splicing regulation, transcription factor binding and enhancer RNA signatures. (ox.ac.uk)
  • We further delineate similarities and differences in epigenetic landscape between stem cell-derived macrophages and primary cells and characterize the context-specific enhancer activities for key innate immune response genes KLF4, SLAMF1 and IL2RA.ConclusionsOur study demonstrates the importance of context-specific macrophage enhancers in gene regulation and utility for interpreting disease associations, providing a roadmap to link genetic variants with molecular and cellular functions. (ox.ac.uk)
  • Transposable elements are able to affect conserved and divergent chromatin looping and contribute to cell- and species-specific gene regulation [ 11 ]. (biomedcentral.com)
  • My research is focused on understanding the regulation of the expression of genes determining complex phenotypes at the molecular level, and their evolution. (inrae.fr)
  • We apply mathematical modeling and experimentation to study gene regulation, molecular transport and interplay between variability and robustness in biological systems. (ecmiindmath.org)
  • Epigenetic dysregulation and disruption of gene enhancer networks are both pervasive in human cancers, and yet, their roles in keratinocyte cancers are poorly understood. (nih.gov)
  • Instead of finding a single clear cause, their results showed large epigenetic disturbances - changes that don't occur in the DNA sequence itself, but are responsible for enhancing or reducing the activity of certain genes. (embl.org)
  • These epigenetic changes can affect the activity of proteins called transcription factors and DNA sequences called enhancers, known as the gene regulatory network. (embl.org)
  • To better understand conservation of enhancer activity, we recently used a comparative genomics approach that integrates temporal expression and epigenetic profiles in an innate immune system. (umassmed.edu)
  • These data suggest that additional genetic, epigenetic, environmental factors, and gene × environment interactions contribute to disease. (biomedcentral.com)
  • We have ongoing interests in the systems level analysis and reconstruction of regulatory networks, inference of enhancer-promoter contacts, predictive models of gene expression and integration of three-dimensional chromatin structure with one-dimensional epigenetic measurements in the context of cancer, malaria, asthma and several autoimmune diseases. (ucsd.edu)
  • The goal of this project is to model the natural variation in gene expression across many immune cell types using an already established database at LJI ( https://dice-database.org ) and to identify cell type-specific epigenetic regulators of important immune genes. (ucsd.edu)
  • To identify epigenetic alterations driving lung adenocarcinoma, we used an improved version of the Tracing Enhancer Networks using Epigenetic Traits method (TENET 2.0) in primary normal lung and lung adenocarcinoma cells. (prolekarniky.cz)
  • To connect enhancer regions to likely target genes, the researchers compared patterns of chromatin activity with gene expression across the 9 cell types. (nih.gov)
  • The scientists were then able to piece together enhancer regulatory networks and their target genes. (nih.gov)
  • The critical functions of TFs in development are coupled to their target genes through TF binding of cis -regulatory elements such as enhancers. (biomedcentral.com)
  • In Hand2-deficient mouse embryos, the EMT underlying AVC cardiac cushion formation is disrupted, and we combined ChIP-seq of embryonic hearts with transcriptome analysis of wild-type and mutants AVCs to identify the functionally relevant HAND2 target genes. (unibas.ch)
  • Since many of these mutations affect elements that control the expression of key determinants of cell fate and phenotype, understanding how these mutations affect the networks that control gene expression opens the way for the development of new classes of drugs. (umassmed.edu)
  • Along with strong driver mutations and passenger mutations predicted to have neutral effects, the team's analysis pointed to a set of passenger mutations suspected of having intermediate effects on genes from immune, metabolic, and other pathways. (genomeweb.com)
  • We observe a mean of 26 somatic single-nucleotide variants per brain present in ≥4% of cells, with enrichment of mutations in coding and putative regulatory regions. (nih.gov)
  • ASD brains show an excess of somatic mutations in neural enhancer sequences compared with controls, suggesting that mosaic enhancer mutations may contribute to ASD risk. (nih.gov)
  • Although mutations or deletions of the SMARCB1 gene play a role in the development of MRT, the events that incite these genetic alterations are unknown. (medscape.com)
  • Mutations and gene deletions causing the thalassemia genotype have arisen independently in different populations but have subsequently propagated by means of natural selection. (medscape.com)
  • More than 20 different genetic mutations resulting in the functional deletion of both pairs of alpha-globin genes (--/--) have been identified. (medscape.com)
  • There are more than 15 different genetic mutations that result in decreased production of alpha globin, usually through functional deletion of 1 or more of the 4 alpha-globin genes. (medscape.com)
  • Better understanding of new mutations and the wide range of possible phenotypes led to the development of a new nomenclature proposal, based on the gene and inheritance pattern. (medscape.com)
  • [ 6 ] However, the gene mutations responsible for the different forms of CMT1 are clearly myelin genes. (medscape.com)
  • Changes in chromatin state can affect how and when genes are expressed. (nih.gov)
  • Four chromatin states were associated with regions known as enhancers, which act at a distance and are not always easy to tie to particular genes. (nih.gov)
  • It shows that there is much more information to be found in the chromatin states of a cell, rather than only looking at gene expression levels," says Judith. (embl.org)
  • Enhancer activation is a multi-step process involving chromatin remodelers and histone modifiers including the monomethylation of H3K4 (H3K4me1) by MLL3 (KMT2C) and MLL4 (KMT2D). (biomedcentral.com)
  • As such, chromatin regulators are an essential part of enhancer function and their dysregulation has severe consequences in development and disease. (biomedcentral.com)
  • Despite the importance of chromatin regulators to human health, we lack fundamental insight into how general chromatin regulators such as MLL3/4 coordinate enhancer function. (biomedcentral.com)
  • Histone modifications and chromatin-associated protein complexes are crucially involved in the control of gene expression, supervising cell fate decisions and differentiation. (researchgate.net)
  • Background: Bivalent chromatin domains consisting of the activating histone 3 lysine 4 trimethylation (H3K4me3) and repressive histone 3 lysine 27 trimethylation (H3K27me3) histone modifications are enriched at developmental genes that are repressed in embryonic stem cells but active during differentiation. (researchgate.net)
  • Our work uses functional genomics DNase-seq, ATAC-seq, ChIP-seq, RNA-seq, MPRA, Hi-C, and chromatin state data to computationally identify combinations of transcription factor binding sites which operate to define the activity of cell-type specific enhancers. (beerlab.org)
  • Transposable elements (TE) are important components of livestock and poultry genomes, contributing to their genetic diversity, chromatin states, gene regulatory networks, and complex traits of economic value. (biomedcentral.com)
  • Positional cloning efforts revealed that this locus contains the SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily B, member 1 ( SMARCB1 ) gene, also known as human sucrose non-fermenting gene number 5 ( hSNF5 ), integrase interactor 1 ( INI1 ) , or 47-Kd Brg1/Bam -associated factor ( BAF47 ). (medscape.com)
  • The integration of this new information with previous findings has allowed us to draw a more complete pathway of regulatory events during cardiac induction and differentiation in Drosophila . (biologists.com)
  • A lncRNA identifies Irf8 enhancer element in negative feedback control of dendritic cell differentiation. (costalab.org)
  • However, many sites gain H3K27ac independent of MLL3/4 or H3K4me1 including enhancers regulating key factors in early differentiation. (biomedcentral.com)
  • Mesectoderm differentiation is controlled by the bHLH-PAS gene, sim . (sdbonline.org)
  • Hedgehog signaling activates a mammalian heterochronic gene regulatory network controlling differentiation timing across lineages. (cincinnatichildrens.org)
  • Embryonic development is driven by a large set of finely orchestrated regulatory programs that control cell fate decisions, differentiation and morphogenesis, leading to formation of a complex organism. (ox.ac.uk)
  • Hematopoietic transcription factors (= gene regulatory proteins) concertedly control cell proliferation, lineage commitment, and cell differentiation. (mdc-berlin.de)
  • During his PhD research, Aerts invented one of the first bioinformatics algorithms for the prediction of genomic enhancers (ModuleSearcher) and developed several bioinformatics tools for the analysis of cis-regulatory sequences (TOUCAN) and for gene prioritisation (Endeavour). (wikipedia.org)
  • Clustering of conserved accessible DNA sequences within enhancers identified shared sequence motifs (including motifs for known factors), as well as many with unknown function. (umassmed.edu)
  • We have performed a promoter analysis searching for potential regulatory sequences of puc and identified different specific enhancers directing gene expression in different tissues and at different developmental times. (preprints.org)
  • These stripes are regulated by a 300-bp enhancer (NEE) that contains high-affinity Dl-binding sites, Twist-binding sites, and "generic" E-box sequences that appear to bind ubiquitously distributed bHLH activators (Daughterless and Scute), which are present in the unfertilized egg. (sdbonline.org)
  • In the current report, a systematic approach is implemented to catalogue regulatory elements within HERVs, as a roadmap to potential functions of HERV sequences in gene networks. (mdpi.com)
  • I analyzed the presence of HERV sequences on consensus cis-regulatory elements (cCREs) from ENCODE data. (mdpi.com)
  • He leads the Laboratory of Computational Biology at VIB and KU Leuven (University of Leuven), and has received several accolades for his research into the workings of the genomic regulatory code. (wikipedia.org)
  • His research focuses on deciphering the genomic regulatory code, using a combination of single-cell, machine-learning, and high-throughput experimental approaches. (wikipedia.org)
  • Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapeutics effective in one cancer type to others with a matching genomic profile, and to construct personalized networks for use in developing combinatorial therapy. (biomedcentral.com)
  • Array comparative genomic hybridization in patient one and patient two revealed copy-number variant (CNV) deletions, respectively, ~ 1.45 Mb in size involving FOXF1 and an ~ 0.7 Mb in size involving FOXF1 enhancer and leaving FOXF1 intact. (researchgate.net)
  • The ultimate goal of our research is to understand how gene regulatory information is encoded in genomic DNA sequence. (beerlab.org)
  • Furthermore, the HAND2-interacting enhancers in the Snai1 genomic landscape are active in embryonic hearts and other Snai1-expressing tissues. (unibas.ch)
  • Fagny M. , Glass K., Kuijjer ML.. (2022) Editorial: Applications and Methods in Genomic Networks. (inrae.fr)
  • Fagny M. , Lin X., Platig J., Quackenbush J.. (2022) Connectivity in eQTL networks dictates reproducibility and genomic properties. (inrae.fr)
  • Understanding the fundamental gene regulatory mechanisms underlying addiction and related behaviors could facilitate more effective treatments. (figshare.com)
  • Studies in several vertebrate models and Drosophila have uncovered a surprising degree of evolutionary conservation of regulatory mechanisms and genes that control early cardiogenesis. (biologists.com)
  • These data challenge current models of enhancer activation and imply distinct mechanisms between stable and dynamically changing enhancers. (biomedcentral.com)
  • We identify and functionally validate regulatory cores (Sox10/Tfap2B/SoxB/Hbox) mediating each programme and elucidate their combinatorial activities with other spatiotemporally specific transcription factors (bHLH/NR). Our global deconstruction of the VNC-GRN in vivo sheds light on critical early regulatory mechanisms that may influence the divergent neural phenotypes in enteric neuropathies. (ox.ac.uk)
  • After irradiation, the expression of DDR-related genes and proteins in ΔNp63α-expressing and control cells was analysed by RT-qPCR, Western blotting, and flow cytometry. (researchsquare.com)
  • Integral nuclear pore proteins bind to Pol III-transcribed genes and are required for Pol III transcript processing in C. elegans. (cincinnatichildrens.org)
  • It controls the interaction network of hundreds of thousands of proteins. (creation.com)
  • Key gene regulatory proteins control cell multiplication and instruct cells to adopt distinct cell fates. (mdc-berlin.de)
  • Currently, we concentrate on the functions of "pioneering transcription factors" CCAAT Enhancer Binding Proteins alpha and beta ( C/EBPα,β ) in development and disease. (mdc-berlin.de)
  • We disclose molecular and functional interactions between regulatory proteins and determine how they orchestrate the complex process of proper gene expression and thereby reveal novel therapeutic targets. (mdc-berlin.de)
  • T]he FunSeq tool assigns a molecular functional impact score to a mutation based on various features," the authors explained, such as "inter-species conservation, gain or break of transcription factor motifs, disruption of known enhancer-gene interactions, and centrality in the gene regulatory or protein-interaction network. (genomeweb.com)
  • Such multi-factorial systems are difficult to decode in vertebrates owing to their complex gene hierarchies and transient dynamic molecular interactions. (ox.ac.uk)
  • Our goal is to understand in which situations genetic variability leads to alteration of molecular phenotype and in which it is buffered due to mutual interactions of network genes. (ecmiindmath.org)
  • Dynamical models based upon known interactions between these master genes, such as mutual antagonism and autoregulation, fail to make the system bistable, a desired feature for robust lineage determination. (lu.se)
  • Notably, CENPA, FOXM1, and MYBL2 are also key regulators of cancer-specific enhancers in breast adenocarcinoma of the basal subtype, but they are associated with distinct sets of activated enhancers. (prolekarniky.cz)
  • We demonstrate that the vast majority of differentially regulated enhancers on acute stimulation are subject to tolerance and that expression quantitative trait loci, disease-risk variants and eRNAs are enriched in these regulatory regions and related to context-specific gene expression. (ox.ac.uk)
  • We found over 32,000 enhancers that appear differentially activated between normal lung and lung adenocarcinoma. (prolekarniky.cz)
  • B) Peak density plots showing that the Sox17 -bound loci are cobound by the histone acetyltransferase Ep300 , a marker of active enhancers. (xenbase.org)
  • Phosphorylated Lamin A/C in the Nuclear Interior Binds Active Enhancers Associated with Abnormal Transcription in Progeria. (cincinnatichildrens.org)
  • scMEGA: single-cell multi-omic enhancer-based gene regulatory network inference. (costalab.org)
  • Cell-type deconvolution analysis using snATAC-seq uncovered a potential role of glial cells in driving the gene regulatory programs associated with addiction-related phenotypes. (figshare.com)
  • These genes were selected based on their role in asthmatic inflammatory processes and History previously reported associations with asthma phenotypes. (cdc.gov)
  • Of these mediators, cytokines play a single nucleotide polymorphisms (SNP) in pro-inflammatory cytokine genes and asthma phenotypes (Che et al. (cdc.gov)
  • A tumor suppressor activity of Drosophila Polycomb genes mediated by JAK-STAT signaling. (uni-freiburg.de)
  • As a model genetic system, we use the Drosophila gap genes, which is a class of segmentation genes controlling the body plan formation during the early embryo development. (ecmiindmath.org)
  • Our present study identifies the Dorsocross T-box genes as key mediators of combined Dpp and Wg signals during this process. (biologists.com)
  • Dynamic network-guided CRISPRi screen identifies CTCF-loop-constrained nonlinear enhancer gene regulatory activity during cell state transitions. (beerlab.org)
  • Forkhead box protein M1 (FOXM1) is a key transcription factor (TF) that regulates a common set of genes related to the cell cycle in various cell types. (mdpi.com)
  • Exposed C57BL/6 mice exhibited a specific network of type I interferon signaling in blood cells and aorta from 4hr to 28d post-exposure The central component of the network was the transcription factor interferon regulatory factor 7 (Irf7), the master regulator of the type I interferon response. (cdc.gov)
  • Modelling stochastically the main processes leading a transcription factor molecule to its specific site on the DNA, we aim to investigate formation of the enhancer molecular configurations in terms of the realistic statistical distribution of probabilities of all possible configurations. (ecmiindmath.org)
  • Experimental hematology, leukemia research, in combination with stem cell research strives to untangle the underlying "grammar" of transcription factor networks. (mdc-berlin.de)
  • Knockdown experiments of FOXM1 and MYBL2 suggest that these factors regulate genes involved in controlling cell cycle progression and cell division. (prolekarniky.cz)
  • Introduction regulate choices of expressed genes as part of the macrophage/ neutrophil lineage. (lu.se)
  • Genes that regulate both the synthesis and the structure of different globins are organized into 2 separate clusters. (medscape.com)
  • Yet, we still know little on how the core components of the pathway interact with additional regulators or how this network modulates cellular responses in the whole organism in homeostasis or during tissue morphogenesis. (preprints.org)
  • Key genes are color coded based on regional expression from fate map in (E). (E) Enriched expression of Sox17 -regulated transcripts. (xenbase.org)
  • Gene regulatory networks that drive cell fate are regulated spatiotemporally by cell-type-specific transcription factors (TFs). (biomedcentral.com)
  • ETV2 primes hematoendothelial gene enhancers prior to hematoendothelial fate commitment. (cincinnatichildrens.org)
  • Central to this is the transient increase in H3K4-trimethylation at developmental genes during G1, thereby creating a 'window of opportunity' for cell-fate specification. (researchgate.net)
  • We have recently made significant progress in understanding how DNA sequence features specify cell-type specific mammalian enhancer activity using machine learning, and how enhancer-gene networks control cell-fate decisions and contribute to human disease. (beerlab.org)
  • This project will focus on developing regulatory network inference methods for the joint analysis of gene expression and histone modification data from several different types of tumor infiltrating lymphocytes, which are gathered from a cohort of patients with solid tumors. (ucsd.edu)
  • We find enrichment for context-specific eQTL involving endotoxin response and specific infections and delineate specific differential regions informative for GWAS variants in inflammatory bowel disease and multiple sclerosis, together with a context-specific enhancer involving a bacterial infection eQTL for KLF4. (ox.ac.uk)
  • We show enrichment in differential enhancers for tolerance involving transcription factors NFκB-p65, STATs and IRFs and prioritize putative causal genes directly linking genetic variants and disease risk enhancers. (ox.ac.uk)
  • Epigenomic analysis reveals a dynamic and context-specific macrophage enhancer landscape associated with innate immune activation and tolerance. (ox.ac.uk)
  • Patterns of activity for enhancer elements, they found, correlated strongly with patterns of expression for the nearest gene. (nih.gov)
  • Using a binary-coding system to identify unique concordant expression patterns among genes, the model resulted in a digital rendering of single-cell gene expression which enables non-invasive prognosis of prostate cancer patients. (biomedcentral.com)
  • The candidate genes exhibit expression patterns in lung and heart similar to that of known PAH risk genes, and most variants occur in conserved protein domains. (biomedcentral.com)
  • At the next level of the hybrid modelling approach, we use dynamical equations of the reaction-diffusion type to describe the spatiotemporal patterns of the target gene expression based on the calculated probability of its activation. (ecmiindmath.org)
  • Genetic variations that lie outside of any known genes can lead to disease. (nih.gov)
  • Fagny M. , Kuijjer ML., Stam M., Joets J., Turc O., Rozière J., Pateyron S., Venon A., Vitte C.. (2021) Identification of Key Tissue-Specific, Biological Processes by Integrating Enhancer Information in Maize Gene Regulatory Networks. (inrae.fr)
  • The new genes were identified based solely on rare deleterious missense variants, a variant type that could not be adequately assessed in either cohort alone. (biomedcentral.com)
  • At least eight novel pediatric candidate genes carrying de novo variants have plausible roles in lung/heart development. (biomedcentral.com)
  • However, the known susceptibility variants are incompletely penetrant, many individuals who carry monogenic risk variants never develop PAH, and a subset of patients have deleterious variants in more than one risk gene. (biomedcentral.com)
  • A method to predict the impact of regulatory variants from DNA sequence. (beerlab.org)
  • The ultimate goal of this approach is to formulate a quantitative map between the genotype (regulatory genetic sequence) and the corresponding molecular phenotype (gene expression level) with the single-nucleotide precision. (ecmiindmath.org)
  • 2020), Sox17 and β-catenin co-occupy Wnt-responsive en. (xenbase.org)
  • Sox17 and β-catenin co-occupy Wnt-responsive enhancers to govern the endoderm gene regulatory network. (xenbase.org)
  • Sox17 and β-catenin co-occupy hundreds of key enhancers. (xenbase.org)
  • In some cases, Sox17 and β-catenin synergistically activate transcription apparently independent of Tcfs, whereas on other enhancers, Sox17 represses β-catenin/Tcf-mediated transcription to spatially restrict gene expression domains. (xenbase.org)
  • A) Venn diagram of Sox17 -bound genes (and associated peaks) from ChIP-seq intersected with Sox17 -regulated genes. (xenbase.org)
  • C) Sox17 -bound genes are enriched in the endoderm . (xenbase.org)
  • For example, active promoter states in skeletal muscle were associated with extracellular structure genes, while active promoter states in lymphoblastoid cells were associated with immune response genes. (nih.gov)
  • The cyclic GMP-AMP synthase (cGAS)-Stimulator of Interferon Genes (STING) pathway is a critical defender to sense various pathogens and trigger innate immunity of mammalian cells. (frontiersin.org)
  • The abnormal behaviour of the lung cells in patients with PAH seems to be caused by a general rewiring of this regulatory network. (embl.org)
  • The results suggested that the rewiring of the regulatory network in the cells surrounding the blood vessels, called endothelial cells, makes it possible for them to differentiate to become smooth muscle cells, which then contribute to the obstruction of the lung arteries. (embl.org)
  • Transcriptomic analysis showed decreased RNA expression of cell cycle-related genes and increased expression of programmed cell death-related genes in sip63 cells compared to scr cells. (researchsquare.com)
  • As ChIP-seq cannot establish physical co-occurrence of two marks on the same allele, admixture of cells that either express (green) or do not express (red) the gene in focus could explain the occurrence of both marks as well as the low expression level in the overall population. (researchgate.net)
  • In contrast, in the case of ''true'' bivalency, virtually all cells in the population carry both marks simultaneously at the promoter in question, leading to low, if any, expression for that gene in all cells. (researchgate.net)
  • Here we show that bivalent domains and chromosome architecture for bivalent genes are dynamically regulated during the cell cycle in human pluripotent cells. (researchgate.net)
  • However, prior to commitment, it has been cells, it is evident that GATA-1 and PU.1 are able to specify observed that many genes are expressed at intermediate or basal erythroid and myeloid cell fates (see [16] and references therein). (lu.se)
  • Serum levels of primary inflammatory mediators were not elevated although oncostatin M, an IL-6 family cytokine and type I interferon enhancer, was increased. (cdc.gov)
  • Gene networks control organism phenotype in health and disease by dynamically processing information introduced by genotype and environment. (ecmiindmath.org)
  • The interdependence of different histone modifications and their depositing enzymes at enhancers has been widely studied, although their mechanistic roles remain controversial. (biomedcentral.com)
  • Fagny M. , Platig J., Kuijjer ML., Lin X., Quackenbush J.. (2020) Nongenic cancer-risk SNPs affect oncogenes, tumour-suppressor genes, and immune function. (inrae.fr)
  • We further show that the number of instances of these motifs is a strong predictor of the responsiveness of a gene to pathogen detection. (umassmed.edu)
  • We interrogate the interplay between variability and robustness at different scales, namely in the context of different network motifs as well as small and well-studied genetic networks controlling the body plan formation in fruit fly. (ecmiindmath.org)
  • Furthermore, identification and dissection of divergent upstream combinatorial regulatory codes has afforded new insights into opposing gene circuits that define canonical and neural NC fates. (ox.ac.uk)
  • The latter pair inherits the state of its upstream master genes and further reinforces the decision due to several feedback loops, thereby leading to irreversible commitment. (lu.se)
  • There are five distinct thresholds of gene activity in response to the Dorsal nuclear gradient in early embryos. (sdbonline.org)
  • Aerts research interest in regulatory genomics and gene regulatory networks cover a wide range of experimental and computational approaches, applied in the context of neuronal development, neurodegeneration, as well as cancer. (wikipedia.org)
  • To understand the role of these changes in the disease, the Zaugg group developed a computational tool to reconstruct an enhancer-based gene regulatory network in a specific cell type, which they applied to their data. (embl.org)
  • In addition to the insights gained into this specific disease, the study also describes a computational tool to generate gene regulatory networks. (embl.org)
  • We are located in the McKusick-Nathans Institute of Genetic Medicine, and the Department of Biomedical Engineering, which has long been a leader in the development of rigorous quantitative modeling of biological systems, and is a natural home for graduate studies in Genomics, Bioinformatics, and Computational Biology at Johns Hopkins, including research in Systems Biology, Machine Learning, and Network Modeling. (beerlab.org)
  • We develop a computational model for the hematopoietic erythroid-myeloid lineage decision, which is determined by a genetic switch involving the genes PU.1 and GATA-1. (lu.se)
  • Therefore, we decided to revisit the prevailing model including the epistatic relationship between MLL3/4 to H3K4me1, H3K27ac, and gene transcription in the context of ESCs transitioning from the naive to formative pluripotent states. (biomedcentral.com)
  • Hematopoietic stem cell lineage choices are decided by genetic networks that are turned ON/OFF in a switch-like manner. (lu.se)
  • For example, mesoderm determinants are activated in the anterior third of the embryo, whereas neurogenic genes are expressed in central regions. (sdbonline.org)
  • Enhancers are essential in defining cell fates through the control of cell-type-specific gene expression. (biomedcentral.com)
  • The bacterial cell is able to control many protein-coding genes (green lines at bottom) with relatively few controls (yellow and purple lines). (creation.com)
  • This suggests that these DNA changes are disrupting important regulatory elements and thus play a role in disease biology. (nih.gov)
  • This indicates that a majority of the regions under selection are non-coding regulatory elements or cis-regulatory elements. (umassmed.edu)
  • Modulation of tissue repair by regeneration enhancer elements. (osuchildrensmusclegroup.org)
  • Transposable elements can be considered as a source of raw material for primitive genomes, tools of genetic innovation, and ancestors of modern genes (e.g., ncRNA) [ 15 ]. (biomedcentral.com)
  • The PE enhancer from the twist promoter region exhibits a similar pattern of expression. (sdbonline.org)
  • The Dorsocross genes are induced within the segmental areas of the dorsal mesoderm that receive intersecting Dpp and Wg inputs. (biologists.com)
  • In all these organisms, cardiac induction in the lateral mesoderm involves the concerted action of signals mediated by Bmp, Wnt and Fgf family members, which act upon cardiogenic genes encoding NK homeodomain, Gata and T-box transcription factors (reviewed by Zaffran and Frasch, 2002 ). (biologists.com)
  • The type I target gene folded gastrulation is activated only in response to peak levels of the Dl gradient, so that expression is restricted to a subdomain of the presumptive mesoderm. (sdbonline.org)
  • However, prior to lineage commitment, genes are primed at low expression levels. (lu.se)
  • The approach points to a framework for lineage commitment studies in general and could aid the search for lineage-determining genes. (lu.se)
  • The scientists found that regulatory regions vary greatly in activity depending on the cell type. (nih.gov)
  • The data sets obtained allow us to annotate the sites of regulatory activity, and consequently assemble and test gene regulatory circuitry that controls given developmental process at the cellular level. (ox.ac.uk)
  • Enhanced Regulatory Sequence Prediction Using Gapped k-mer Features. (beerlab.org)
  • This approach incorporates methods of statistical thermodynamics to calculate the activation probability of the target gene taking into account information about its regulatory genetic sequence (enhancers) and the transcription factors regulating the gene expression. (ecmiindmath.org)
  • The HAND2 target gene regulatory network (GRN) includes most genes with known functions in EMT processes and AVC cardiac cushion formation. (unibas.ch)