• Here we report that the atypical kinase RIOK2 (right open reading frame kinase 2) is a master transcription factor (TF) that not only drives erythroid differentiation, but also simultaneously suppresses megakaryopoiesis and myelopoiesis in primary human stem and progenitor cells. (bvsalud.org)
  • Although studies have identified several miRNAs that regulate erythroid commitment and differentiation, we do not understand the mechanism by which the crucial erythroid transcription factors, GATA-1and NF-E2 directly regulate and control differentiation via miRNA pathways. (molcells.org)
  • Taken together, our results establish a functional link among the erythroid transcription factors GATA-1/NF-E2, miR-199b-5p and c-Kit, and provide new insights into the coupling of transcription and post-transcription regulation in erythroid differentiation. (molcells.org)
  • The up-regulation of miR-199b-5p during erythroid differentiation was dependent on the binding of GATA-1 and NF-E2 to its gene locus, which activated its transcription and maintained its high expression level in mature erythroid cells. (molcells.org)
  • The MYC proto-oncogene is a transcription factor essential in stem/progenitor cell maintenance and differentiation [ 11 ]. (nature.com)
  • 9 ) The gene, located on chromosome X ( Xp11.23 ), encodes a key haematopoietic transcription factor involved in erythroid and megakaryocyte differentiation. (smj.org.sg)
  • In development, lineage-restricted transcription factors simultaneously promote differentiation while repressing alternative fates. (prolekarniky.cz)
  • Here, we have analyzed cis element regulation of the critical hematopoietic factor Gata2 , which is expressed in early precursors and repressed as GATA-1 levels rise during terminal differentiation. (prolekarniky.cz)
  • Although Gata2 is normally repressed in late-stage erythroblasts, the −1.8 kb mutation unexpectedly resulted in reactivated Gata2 transcription, blocked differentiation, and an aberrant lineage-specific gene expression pattern. (prolekarniky.cz)
  • In this group of CGIs, repressive polycomb group (PcG) complexes act to block transcription in inappropriate lineages or at non-expressing stages during the differentiation programme. (biomedcentral.com)
  • In this study, we identified zinc finger transcription factor 148 ( ZNF148 , also called Zfp148 and ZBP-89) as a direct target of MYC. (nature.com)
  • BRCA2 gene promoter has bi-directional activity, expressing BRCA2 and a novel C4-type zinc finger containing transcription factor ZAR2. (biomedcentral.com)
  • To obtain structural information, we synthesized single and double zinc finger peptides from the yeast transcription activator ADR1, and assessed the metal-binding and DNA-binding properties of these peptides, as well as the solution structure of the metal-stabilized domains, with the use of a variety of spectroscopic techniques. (embl.de)
  • The mesenchymal phenotype is associated with high expression levels of Snai1, a zinc-finger transcription factor that regulates metastasis by down-regulating the expression of genes such as E-cadherin ( 17 ). (iiarjournals.org)
  • Our lab has previously identified the first non-ribosomal protein mutations in DBA in the erythroid transcription factor GATA1 (Sankaran et al. (simplyblood.org)
  • Nature Medicine, 2014) and was subsequently able to show that ribosomal protein haploinsufficiency results in selective impairment of GATA1 mRNA translation (Ludwig et al. (simplyblood.org)
  • In 2014, Dr. Crispino suggested that in MF abnormal TPO signaling induces a ribosomal deficiency hampering GATA1 mRNA translation in MK. (refine.bio)
  • These pathways involve mTOR-dependent activation of the 70 kDa ribosomal protein S6 kinase (p70S6K) as well as the inactivation of the repressor of mRNA translation, eukaryotic initiation element 4E (eIF4E) binding protein (4EBP) [1,2]. (researchensemble.com)
  • Both disorders are characterised by recurring truncating somatic mutations of the GATA1 gene, which are considered key pathogenetic events. (smj.org.sg)
  • We herein report, to our knowledge, the first observation on the frequency and nature of GATA1 gene mutations in a cohort of Malaysian children with DS-associated TAM (n = 9) and ML-DS (n = 24) encountered successively over a period of five years at a national referral centre. (smj.org.sg)
  • Of the 29 patients who underwent GATA1 analysis, GATA1 mutations were observed in 15 (51.7%) patients, including 6 (75.0%) out of 8 patients with TAM, and 9 (42.9%) of 21 patients with ML-DS. (smj.org.sg)
  • The low frequency of GATA1 mutations in ML-DS patients is unusual and potentially indicates distinctive genomic events in our patient cohort. (smj.org.sg)
  • 8 ) An additional shared, critical pathogenetic event involves the acquisition of characteristic somatic mutations in the GATA1 gene. (smj.org.sg)
  • These mutations, involving exons 2 or 3 of the GATA1 gene, result in synthesis of an aberrant truncated isoform (termed short GATA1 or GATA1s ) that is putatively oncogenic. (smj.org.sg)
  • 10 ) The mechanistic basis for somatic GATA1 mutations and the additional molecular events that determine progression from TAM to ML-DS are the focus of intense research. (smj.org.sg)
  • This observational study attempts to characterise, for the first time, to our knowledge, the frequency and nature of somatic GATA1 mutations in DS children with TAM and ML-DS, encountered consecutively over a period of five years at a national paediatric oncology referral centre in Malaysia. (smj.org.sg)
  • Previously, we observed that transcription factor RUNX1 mutations ( RUNX1 -MT) coexisted with ASXL1 -MT in CMML and at myeloid blast phase of chronic myeloid leukemia. (biomedcentral.com)
  • Thus, FLI1 drives tumor metastasis not only through the canonical oncoprotein pathway, but also by using epigenetic mechanisms mediated by its exonic circular RNA. (biomedcentral.com)
  • These features are associated with efficient translation in unperturbed conditions and among hematopoietic master regulators relatively uniquely exhibited by GATA1, a key transcription factor of erythropoiesis. (simplyblood.org)
  • Our study reveals the previously uncharacterized winged helix-turn-helix DNA-binding domain and two transactivation domains of RIOK2 that are critical to regulate key hematopoietic TFs GATA1, GATA2, SPI1, RUNX3 and KLF1. (bvsalud.org)
  • Importantly, RIOK2 mRNA expression significantly correlates with these TFs and other hematopoietic genes in myelodysplastic syndromes, acute myeloid leukemia and chronic kidney disease. (bvsalud.org)
  • However, little is known about the molecular mechanisms underlying the aberrant activation of FLI1 in these solid tumors. (biomedcentral.com)
  • Increased expression of inflammatory cytokines, lysyl oxidase, transforming growth factor-β, impaired megakaryocyte function, and aberrant JAK-STAT signaling have all been implicated in the pathogenesis of bone marrow fibrosis. (haematologica.org)
  • In this study, we examined whether AdipoR mRNA expression in human myotubes correlates with in vivo measures of insulin sensitivity. (diabetesjournals.org)
  • They found that limited availability of ribosomes differentially affects mRNA transcripts, and especially reduces translation of transcripts with short or unstructured 5' UTRs that are necessary for erythropoiesis. (simplyblood.org)
  • By analyzing the methylomes and transcriptomes of 14 fetal and 181 adult livers, we identified 657 differentially methylated genes with adult-specific expression, these genes were enriched for transcription factor binding sites of HNF1A and HNF4A. (biomedcentral.com)
  • mRNA-Seq revealed 1,107 significantly differentially expressed genes, 73 of which were increased 15 DPP and 1,034 were increased 30 DPP. (biomedcentral.com)
  • For example, GATA-1 directly represses Gata2 transcription via displacing GATA-2 from chromatin sites at its own locus, a process termed a "GATA Switch" [6] , [7] . (prolekarniky.cz)
  • Description: The AFS98 monoclonal antibody reacts with the mouse CD115 molecule, a receptor for macrophage colony stimulating factor (M-CSF) or colony stimulating factor-1 (CSF-1). (thermofisher.com)
  • These diverse actions of glucocorticoids are mediated by the glucocorticoid receptor (GR), which belongs to the nuclear receptor superfamily and functions as a hormone-dependent transcription factor. (brainimmune.com)
  • This has led to an improved understanding of the multilayered mechanisms of this pathway transduction proceeds as well as the molecular mechanism regulating this pathway ( 28 ). (frontiersin.org)
  • Mechanistically, the CCL20/CCR6 signaling pathway upregulates HIF-1α by stimulating nuclear factor kappa B-driven transactivation of the HIF1A gene. (cancerindex.org)
  • The notion could be that unique cellular mechanisms are triggered in the breast cancer cells to stimulate BRCA2 gene expression as a temporary measure to regulate the growth of the breast cancer cells. (biomedcentral.com)
  • Since glucocorticoids are essential for life, other cellular signaling pathways strongly regulate GR actions in many different ways, such as physical interaction via their effector transcription factors and epigenetic modifications including phosphorylation and acetylation. (brainimmune.com)
  • The mechanism by which protein complexes interact to regulate the deposition of post-translational modifications of histones remains poorly understood. (biomedcentral.com)
  • A greater understanding of the molecular abnormalities underlying PC progression and the associated mechanisms responsible for treatment resistance may reveal potential biomarkers related to treatment failure, adding a valuable tool to the clinician's arsenal. (oaepublish.com)
  • Molecular dissection of this process has been challenging as transcription factor loci are regulated by many trans -acting factors functioning through dispersed cis elements. (prolekarniky.cz)
  • SUMOylation of proteins is an important mechanism in cellular responses to environmental stress ( 21 , 22 ). (frontiersin.org)
  • While transcription factors bind and recruit chromatin-modifying and remodeling proteins, the relative contribution of individual cis elements residing within clusters of cis elements to the transcriptional control of endogenous loci is incompletely understood. (prolekarniky.cz)
  • Their studies centered on mice missing delicate mental retardation gene (FMR1), which is another proteins that affects translation mRNA. (researchensemble.com)
  • The reverse activity transcribes the ZAR2 mRNA with 966 nt coding sequence which codes for a 321 amino acid protein. (biomedcentral.com)
  • A significant reduction in protein and/or mRNA expression of CHCHD2 was confirmed in PD brains collected at autopsy as well as in the brains of a PD animal model overexpressing α-synuclein, in addition to seeing a reduction of CHCHD2 in erythrocytes of the same animals. (biomedcentral.com)
  • Summary We conclude that mTOR has a part in maintaining prolonged pain claims via mRNA translation and thus protein synthesis. (researchensemble.com)
  • The CDK4-cyclinD complex normally phosphorylates the retinoblastoma protein (Rb protein), leading to release of the E2F transcription factor and cell cycle progression. (medscape.com)
  • Erythrocytic CHCHD2 mRNA was significantly reduced even at the early stages of the disease. (biomedcentral.com)
  • The covalent modification of histones to yield specific histone marks promotes either the activation or repression of transcription [3] . (prolekarniky.cz)
  • Overexpression of α-synuclein in cellular models of PD also resulted in reduced CHCHD2, via mechanisms likely involving altered subcellular localization of p300 histone acetyltransferase. (biomedcentral.com)
  • the tasks of local rapamycin-sensitive pathways at the level of the hind paw inside a model of nerve injury [6] or the time-restricted tasks of rapamycin-sensitive pathways in hippocampal long term potentiation (LTP) [7] expose insights into the possible roles these mechanisms perform in the peripheral and central nervous system. (researchensemble.com)
  • More recently, Co-workers and Cost have got implicated particular spine mRNA translation pathways in formalin-induced behavioural hypersensitivity [9]. (researchensemble.com)
  • We also identified 1,000 genes specific to fetal liver, which were enriched for GATA1, STAT5A, STAT5B and YY1 binding sites. (biomedcentral.com)
  • In particular, such mechanisms can influence the expression of hepatic ADME genes. (biomedcentral.com)
  • Nineteen candidate genes selected from mRNA-Seq results, were independently assessed by qRT-PCR in additional postpartum cows (5 animals) at both time points. (biomedcentral.com)
  • Transcription factors in these networks occupy specific cis elements at target gene loci where they modulate chromatin remodeling and modification, and thereby transcription. (prolekarniky.cz)
  • However, the mechanisms underlying the regulation of SIRT6 in tumorigenesis remain elusive. (bvsalud.org)
  • Our analyses generated a comprehensive resource of factors involved in the regulation of hepatic gene expression, and allowed us to estimate the proportion of variation in gene expression that could be attributed to genetic and epigenetic variation, both crucial to understanding differences in drug response and the etiology of liver diseases. (biomedcentral.com)
  • GATA factor cross-regulation represents an instructive model system for investigating the contribution of individual cis elements to the initiation and maintenance of transcriptional repression. (prolekarniky.cz)
  • While BRCA2 expression is involved in cell cycle checkpoints and DNA repair, the mechanisms of cell cycle-dependent regulation of BRCA2 gene expression remains elusive. (biomedcentral.com)
  • Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors and commonly play an important role in the regulation of lipid homeostasis. (biomedcentral.com)
  • AdipoR1 mRNA expression was positively correlated with in vivo insulin and C-peptide concentrations, first-phase insulin secretion, and plasma triglyceride and cholesterol concentrations before and after adjustment for sex, age, waist-to-hip ratio, and body fat. (diabetesjournals.org)
  • Expression of AdipoR2 mRNA clearly associated only with plasma triglyceride concentrations. (diabetesjournals.org)
  • In multivariate linear regression models, mRNA expression of AdipoR1, but not AdipoR2, was a determinant of first-phase insulin secretion independent of insulin sensitivity and body fat. (diabetesjournals.org)
  • However, there is substantial inter-individual variation in hepatic gene expression, and although numerous genetic factors have been identified, less is known about the epigenetic factors. (biomedcentral.com)
  • GATA factors are often expressed in an overlapping but reciprocal pattern, such that expression of one GATA factor increases as expression of another decreases. (prolekarniky.cz)
  • As a transcription factor whose expression is increased by DNA damage, p53 blocks cell division at the G1 phase of the cell cycle to allow DNA repair. (medscape.com)
  • However, little is known about the mechanisms underlying the activation of this proto-oncogene in tumors. (biomedcentral.com)
  • By contrast, Hepatocyte growth factor (Hgf), a well-known promoter of epithelial-mesenchymal transitions and a prime target of Matriptase1 activity, plays no major role. (biologists.com)
  • Yet, despite these groundbreaking studies by our colleagues, tangible post-transcriptional mechanisms regulating lineage-commitment from HSPCs were mostly not elucidated. (simplyblood.org)
  • Friend leukemia virus integration 1 (FLI1), an ETS transcription factor family member, acts as an oncogenic driver in hematological malignancies and promotes tumor growth in solid tumors. (biomedcentral.com)
  • Bennett J, Baumgarten SC, Stocco C. GATA4 and GATA6 Silencing in Ovarian Granulosa Cells Affects Levels of mRNAs Involved in Steroidogenesis, Extracellular Structure Organization, IGF-I Activity, and Apoptosis. (chicagobiomedicalconsortium.org)
  • GATA factor function has been extensively studied in the context of hematopoiesis, where GATA-1, GATA-2, and GATA-3 are key regulators. (prolekarniky.cz)
  • This is attained by spinally administering the overall transcription inhibitor actinomycin D and the overall translation inhibitor anisomycin spinally, to formalin shot in to the hind paw prior. (researchensemble.com)
  • Support for MK GATA1 deficiency as phenotypic modifier in MF was provided by the observation that mice carrying the Gata1low mutation reducing Gata1 transcription in MK develop myelofibrosis. (refine.bio)
  • In Gata1low and wild-type mice, TPO mRNA was expressed by bone marrow (BM), spleen and liver. (refine.bio)
  • Ethanol consumption inhibits metastasis of melanoma in mice, but the mechanism is not well understood. (iiarjournals.org)
  • Considering that each microRNA regulates up to hundreds of different mRNAs, and that each mRNA is regulated by tens of microRNAs, this finding adds a new layer of complexity to the regulatory dynamics of the human transcriptome. (pharmaceuticalintelligence.com)
  • Therefore, there is a need to understand the mechanism by which melanomas metastasize so that better preventative and treatment strategies can be established. (iiarjournals.org)
  • Human APP mRNA was detected in neurons and neuronal processes, but not in vessel walls. (findzebra.com)
  • One major problem in current synthetic biology research is designing and controlling the synthetic circuits to perform reliable and robust behaviors as they utilize common transcription and translational resources among the circuits and host cells. (sontaglab.org)
  • Hypoxia stimulates cancer cells to acquire a more malignant phenotype via activation of hypoxia-inducible factor 1 (HIF-1). (cancerindex.org)
  • To investigate the effects of changing the composition of TFIID in a simple system we depleted TAF1 from Drosophila cells and determined the consequences on metal induced transcription at an inducible gene, Metallothionein B (MtnB). (refine.bio)
  • We observe a marked increase in the levels of both the mature message and pre-mRNA in TAF1 depleted cells. (refine.bio)
  • These new results expand the selection of treatment strategies in PC, thus prompting the need to identify predictive factors to select ideal candidates for anticipated therapies. (oaepublish.com)
  • In terms of diseases, Caries is a multifactorial disease and little is still known about the host genetic factors influencing susceptibility. (wikipedia.org)
  • Gata1low livers expressed TPO mRNA levels 6-fold greater than wild-type livers. (refine.bio)
  • Such differences can be used to eliminate candidate competition mechanisms when constructing models based on given data. (sontaglab.org)
  • With knowledge of physics laws and underlying mechanisms, the dynamical behaviors of the synthetic circuits can be described by the first principle models, usually represented by a system of ordinary differential equations (ODEs). (sontaglab.org)
  • MF is also associated with reduced GATA1 content in MK suggesting that this abnormality represents a phenotypic modifier. (refine.bio)
  • Notably, FECR1 utilizes a positive feedback mechanism to activate FLI1 by inducing DNA hypomethylation in CpG islands of the promoter. (biomedcentral.com)
  • However mechanisms that control inflammation and achieve a physiologically functioning endometrium, while avoiding disease in the postpartum cow are not succinctly defined. (biomedcentral.com)
  • There is a long-standing appreciation for the importance of the spatial and temporal control of transcription. (refine.bio)
  • 2015). Mechanisms for cheater control have been described and include kin-selection (Diggle et al. (antiviralbiologic.com)
  • When is definitely cultivated continually on casein, Vargatef inhibitor LasR-mutant cheaters, which produce neither elastase nor additional quorum-regulated factors, emerge (Sandoz et al. (antiviralbiologic.com)
  • Under conditions of continued metal exposure, we show that TAF1 depletion increases the magnitude of the initial transcription burst, but has no effect on the timing of that burst. (refine.bio)
  • There are 431 different transcription binding factor sites, some of these binding factors include GATA1, TGIF, LMX1A, and NKX61 There are no known micro-RNA targets in the 3' UTR. (wikipedia.org)