• Most genes are associated with factors that establish and release paused Pol II and therefore appear to progress through this step, although only a subset of genes appears to be directly regulated by pausing. (nature.com)
  • Another mechanism, interaction of enhancer RNA with NELF, causes dissociation of NELF from RNA polymerase II, resulting in productive elongation of mRNA, as studied in two immediate early genes. (wikipedia.org)
  • The coordinated transcription of genes involves the regulated release of RNA polymerase II (RNAPII) from promoter-proximal sites into active elongation. (nih.gov)
  • Moreover, we find that PAF1C promotes RNAPII pause release in promoter-proximal regions and subsequently acts as a processivity factor that stimulates transcription elongation throughout genes. (nih.gov)
  • We assign transcription initiation sites to 7691 protein-coding genes and find that they display features typical of eukaryotic promoters. (nih.gov)
  • It is transcriptional activator that recognizes and binds to the sequence 5'-RTTAYGTAAY-3' found in the promoter of genes such as albumin, CYP2A4 and CYP2A5. (avivasysbio.com)
  • This synthetic genetic interaction is seen at the level of single genes and acts downstream of promoter nucleosome reorganization. (sdbonline.org)
  • With the development of RNA sequencing and microarray technology, the study of differentially expressed genes (DEGs) between cancer and normal tissues has improved our understanding of the molecular mechanism of PTC. (peerj.com)
  • We revealed 3 hub genes, including one up-regulated gene VEGFA and two down-regulated genes JUN and FOS, which are closely related to the development of PLA2R-associated IMN. (biomedcentral.com)
  • The role of promoter proximal pausing of RNA polymerase II, which regulates transcription of several developmental genes by GAGA factor or Motif 1 Binding Protein (M1BP), has not been fully understood in cellular homeostasis. (udayton.edu)
  • While acetylated histones are found primarily at promoters of actively transcribed genes, they can also be found throughout the active gene [ 8 ]. (biomedcentral.com)
  • Finally, using electrophoretic mobility shift assay, we have identified YYl-related factors that bind to two other transcription initiators in cellular genes. (princeton.edu)
  • Furthermore, these two genes are modulators in clusters C4 and C5, abundant in cytokine/chemokine signalling and Jak-STAT signalling pathways. (springeropen.com)
  • In molecular biology, the NELF (negative elongation factor) is a four-subunit protein complex (NELF-A, NELF-B, NELF-C/NELF-D, and NELF-E) that negatively impacts transcription by RNA polymerase II (Pol II) by pausing about 20-60 nucleotides downstream from the transcription start site (TSS). (wikipedia.org)
  • Directed elongation from an upstream enhancer toward a downstream gene could potentially deliver RNA polymerase II to a proximal promoter, or alternatively might function directly as a distal promoter. (nih.gov)
  • These include upstream and downstream promoter-proximal elements, enhancers, repressers, and silencers, which modulate the rate of specific initiation by RNA polymerase II. (princeton.edu)
  • We speculate that by coupling RNA processing to the status and activity of Pol II itself, the cell ensures that nascent RNA is properly protected from degradation and efficiently matures into a functional mRNA. (nature.com)
  • Core, L. J., Waterfall, J. J. & Lis, J. T. Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters. (nature.com)
  • In SR-2211 particular, it has been shown the Pol II CTD interacts with splicing factors and could be a landing platform favoring the connection of these splicing factors with the nascent RNA (6, 14, 27, 36, 42). (thetechnoant.info)
  • The known mechanistic features of Pol II pausing and its release to productive elongation are described. (nature.com)
  • Recent years have witnessed a sea change in our understanding of transcription regulation: whereas traditional models focused solely on the events that brought RNA polymerase II (Pol II) to a gene promoter to initiate RNA synthesis, emerging evidence points to the pausing of Pol II during early elongation as a widespread regulatory mechanism in higher eukaryotes. (nature.com)
  • We present evidence that loss of FACT has a dramatic impact on Pol II elongation-coupled processes including histone H3 lysine 4 (H3K4) and H3K36 methylation, consistent with a role for FACT in coordinating histone modification and chromatin architecture during Pol II transcription. (open.ac.uk)
  • NELF also works with DSIF to inhibit the speed of Pol II during the elongation phase in transcription. (wikipedia.org)
  • P-TEFb (positive transcription elongation factor b) inhibits the effect of NELF and DSIF on Pol II elongation, via its phosphorylation of serine-2 of the C-terminal domain of Pol II, and the SPT5 subunit of DSIF, causing dissociation of NELF. (wikipedia.org)
  • The subsequent synergistic regulation of POL II carboxyterminal domain (CTD) phosphorylation by BRD4 and RPAP2 initiated ZBTB16 transcriptional elongation, which facilitated MSC osteogenesis via the key osteogenic transcription factor SP7. (nature.com)
  • After the binding of the RPAP2-Pol II complex to BRD4 on SEs, RPAP2 dephosphorylates Ser5 at the Pol II CTD to terminate the transcriptional pause, and BRD4 phosphorylates Ser2 at the Pol II CTD to initiate transcriptional elongation, which synergistically drives efficient transcription of ZBTB16, ensuring proper osteogenesis. (nature.com)
  • While unphosphorylated forms of Pol II are loaded on gene promoters, Ser5 and Ser2 phosphorylation must occur to permit transcription initiation and elongation, respectively (39, 44). (thetechnoant.info)
  • Mechanism of selective recruitment of RNA polymerases II and III to snRNA gene promoters. (icr.ac.uk)
  • When triggered by ligands, nuclear receptors bind to their target gene promoters and serve as platforms for the subsequent recruitment of transcriptional coregulators (for a recent review, see research 33). (thetechnoant.info)
  • PAF1C is dispensable for TCR-mediated repair, but is essential for recovery of RNA synthesis after UV irradiation, suggesting an uncoupling between DNA repair and transcription recovery. (nih.gov)
  • Gene expression is definitely a multistep process starting SR-2211 in the nucleus with the synthesis of premessenger RNAs (pre-mRNAs) and with RNA processing (including 5- and 3-end processing and splicing). (thetechnoant.info)
  • Pausing provides a point of regulation that is distinct from Pol II recruitment and initiation, and this may facilitate the integration of multiple cellular signals. (nature.com)
  • We characterized the landscape of RNA Pol II transcription initiation, identifying 73,500 distinct clusters of initiation. (nih.gov)
  • In particular, there are incremental examples of the participation of the distinct class of long non-coding RNAs (lncRNAs) in AML epigenetic regulation, some of which have translational potential. (frontiersin.org)
  • Akin to the normal hematopoietic system, leukemias are sustained by a small number of leukemia stem-like cells (LSC), which can be distinct from the normal hematopoietic stem cells (HSC) but also exhibit functional characteristics of self-renewal and (abnormal or hindered) differentiation, and are often quiescent ( 2 - 4 ). (frontiersin.org)
  • It has two known alternative splice variants with distinct isoforms though presence of other isoforms cannot be excluded. (thermofisher.com)
  • The human GR is a modular protein composed of distinct regions illustrated in panel B in the image below, as follows: (1) The amino-terminal A/B region, also called immunogenic or N-terminal domain (NTD) and (2) the C, D, and E regions, which correspond to the DNA-binding domain, the hinge region, and the ligand-binding domain, respectively. (medscape.com)
  • Pol II pausing and release occur at a point when 5′ end RNA processing and phosphorylation of the Pol II carboxy-terminal domain occurs. (nature.com)
  • The mechanism involved in cotranscriptional splicing depended on the level of serine 5 phosphorylation of RNA polymerase II in the gene 5 end and on the recruitment of CBP80, one of the two subunits of the cap binding complex, which stimulates splicing of the promoter-proximal intron. (thetechnoant.info)
  • The Pol II CTD is composed of 52 repeats of a conserved heptapeptide motif (YSPTSPS) that is subject to phosphorylation at serine 5 (Ser5) and serine 2 (Ser2) (39, 44). (thetechnoant.info)
  • Figure 2: Patterns of Pol II distribution across gene regions. (nature.com)
  • Through proteomics screens, we find that the TCR-specific CSB protein loads the evolutionary conserved PAF1 complex (PAF1C) onto RNAPII in promoter-proximal regions in response to DNA damage. (nih.gov)
  • These and other PTMs generate a combinatorial histone code that demarcates chromatin regions for transcription activation or repression [ 2 ]. (biomedcentral.com)
  • Integrator endonuclease drives promoter-proximal termination at all RNA polymerase II-transcribed loci. (rochester.edu)
  • The Streptococcus pyogenes Cas9 (SpCas9) nuclease can be efficiently targeted to genomic loci by means of singleguide RNAs (sgRNAs) to enable genome editing 1 - 10 . (cdc.gov)
  • Lis, J. Promoter-associated pausing in promoter architecture and postinitiation transcriptional regulation. (nature.com)
  • These findings bring to light a broader role for FACT in the regulation of Pol II transcription. (open.ac.uk)
  • Furthermore, site-directed mutagenesis and deletion analysis revealed that the proximal GC-rich motifs at -223 and -214 are critical for the ER beta-induced ER alpha down-regulation in breast cancer cells. (unical.it)
  • However, the molecular mechanisms underlying the potential opposing roles played by the two estrogen receptors on tumor cell growth remain to be elucidated. (unical.it)
  • ABSTRACT This study aimed to estimate the frequency of the SNPs (+45T>G and +276G>T) genotypes and investigate the association between the two SNPs and adiponectin concentration, metabolic parameters and risk of T2DM in the Bahraini population. (who.int)
  • FACT (facilitates chromatin transcription) is an evolutionarily conserved histone chaperone that was initially identified as an activity capable of promoting RNA polymerase II (Pol II) transcription through nucleosomes in vitro. (open.ac.uk)
  • This occurred through ER beta-Sp1 protein-protein interactions within the ER alpha promoter region and the recruitment of a corepressor complex containing the nuclear receptor corepressor NCoR, accompanied by hypoacetylation of histone H4 and displacement of RNA-polymerase II. (unical.it)
  • The protein encoded by this gene belongs to the EGR family of Cys 2 His 2 -type zinc finger proteins. (wikipedia.org)
  • The AF-1 plays an important role in the interaction of the receptor with molecules necessary for the initiation of transcription, such as coactivators, chromatin modulators, and basal transcription factors, including RNA polymerase II, TATA-binding protein (TBP), and a host of TBP-associated proteins (TAFIIs). (medscape.com)
  • Multiple lines of evidence support the idea that Pol II and nucleosomes compete for promoter binding and suggest that a crucial role of paused Pol II involves maintenance of accessible promoter chromatin architecture. (nature.com)
  • RNA polymerase transcription initiation sites are largely unknown in Caenorhabditis elegans. (nih.gov)
  • In addition, the promoter-proximal region between -45 and +30 (relative to the start of initiation) contains two highly conserved motifs, the TATA sequence at around -30 and CA at +1 (ref. 4). (princeton.edu)
  • Non (protein)-coding RNAs are the most abundant transcriptional products of the coding genome, and comprise several different classes of molecules with unique lengths, conformations and targets. (frontiersin.org)
  • RNA polymerase III (RNAPIII) synthesizes essential and abundant noncoding RNAs such as transfer RNAs. (icr.ac.uk)
  • The aim of this mini-review is to discuss emerging epigenetic roles of long non-coding RNAs (lncRNAs) in Acute Myeloid Leukemia (AML). (frontiersin.org)
  • Knockout studies in mice suggested the roles of this gene in differentiation of T helper 2 (Th2) cells, expression of cell surface markers, and class switch of immunoglobulins. (ucsc.edu)
  • Transient transfection experiments, using a vector containing the human ER alpha promoter region, showed that elevated levels of ER beta down-regulated basal ER alpha promoter activity. (unical.it)
  • In contrast, we proven for the first time that despite a strong transcriptional activation of the gene, the production of mRNA is not optimized owing to inefficient cotranscriptional RNA processing. (thetechnoant.info)
  • Alternative splicing of the primary transcript gives rise to the 2 mRNA and protein isoforms, hGR-alpha and hGR-beta. (medscape.com)
  • A growing body of evidence indicates that epigenetic regulators rely, amongst other factors, on their interaction with untranslated RNA molecules for guidance to particular targets on DNA. (frontiersin.org)
  • Mechanistically, SEs recruited bromodomain containing 4 (BRD4) at the site of ZBTB16 , which then bound to RNA polymerase II-associated protein 2 (RPAP2) that transported RNA polymerase II (POL II) into the nucleus. (nature.com)
  • RPAP2 transports RNA Pol II from the cytoplasm to the nucleus and guides Pol II to target ZBTB16 via recognition of the navigator BRD4 on SEs. (nature.com)
  • The nomenclature of different promoter-associated RNA polymerase II (Pol II) species is explicitly defined in an effort to provide consistency in future literature. (nature.com)
  • Pausing is now recognized to be a pervasive feature of promoters in mammals and Drosophila melanogaster , and the evidence supporting this from genome-wide studies is presented. (nature.com)
  • In this report, we describe a global analysis of FACT function in Pol II transcription in Drosophila. (open.ac.uk)
  • This data suggests that the cellular homeostasis response demonstrated by two independent cell death mechanisms, apoptosis and autophagy, can be regulated by a common transcriptional pausing mechanism orchestrated by M1BP. (udayton.edu)
  • Fluorogenic RNA aptamers are synthetic functional RNAs that specifically bind and activate conditional fluorophores. (icr.ac.uk)
  • The NELF has four subunits within its complex which are the following: NELF-A, NELF-B, NELF-C/NELF-D, and NELF-E. The NELF-A subunit is encoded by the gene WHSC2 (Wolf-Hirschhorn syndrome candidate 2). (wikipedia.org)
  • NELF binds in a stable complex with DSIF (5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRB)-sensitivity inducing factor) and RNA polymerase II together, but not with either alone. (wikipedia.org)
  • Interactions by subunit: NELF-A: Pol II complex. (wikipedia.org)
  • NELF undergoes Phase separation in vitro and Condensation in vivo The NELF complex is also possibly a player in the enlistment of gene PCF11 to the stopped Pol II in HIV-1 latency. (wikipedia.org)
  • PolyAMiner-Bulk: A Machine Learning Based Bioinformatics Algorithm to Infer and Decode Alternative Polyadenylation Dynamics from bulk RNA-seq data. (rochester.edu)
  • Importantly, we identify a role for FACT in the maintenance of promoter-proximal Pol II pausing, a key step in transcription activation in higher eukaryotes. (open.ac.uk)
  • Large Stokes shift fluorescence activation in an RNA aptamer by intermolecular proton transfer to guanine. (icr.ac.uk)
  • Mammalian lipid homeostasis requires proteolytic activation of membrane-bound sterol regulatory element binding protein (SREBP) transcription factors through sequential action of the Golgi Site-1 and Site-2 proteases. (thebiogrid.org)
  • FUNCTION: Catalyzes the attachment of serine to tRNA(Ser) in a two-step reaction: serine is first activated by ATP to form Ser- AMP and then transferred to the acceptor end of tRNA(Ser) (PubMed:22353712, PubMed:24095058, PubMed:9431993, PubMed:26433229, PubMed:28236339). (genebe.net)
  • Comorbid type 2 diabetes mellitus (T2DM) increases the risk for tuberculosis (TB) and its associated complications, although the pathological connections between T2DM and TB are unknown. (springeropen.com)
  • Amongst those, one of the major public health concerns in present decade is the adverse effect of acquired host-derived factors like type 2 diabetes mellitus (T2DM) that increases the risk and severity of TB. (springeropen.com)
  • We genotyped the two ADIPOQ SNPs in 140 unrelated T2DM patients and 66 nondiabetic controls using the polymerase chain reaction-restriction fragment length polymorphism assay. (who.int)
  • The more negative the energy, the more secondary structure the RNA is likely to have. (ucsc.edu)
  • Thus, it is reasonable to suggest that a dysregulation of the two estrogen receptor subtypes may induce breast cancer development. (unical.it)
  • However, a growing body of evidence suggests that recruitment, stability, and function of epigenetic factors can be mediated by non-protein-coding RNAs. (frontiersin.org)
  • Beside its function in the nervous system, there is significant evidence that EGR-1 along with its paralog EGR-2 is induced in fibrotic diseases has key functions in fibrinogenesis and is necessary for experimentally induced fibrosis in mice. (wikipedia.org)
  • The DNA-binding domain of EGR-1 consists of three zinc finger domains of the Cys 2 His 2 type. (wikipedia.org)
  • We have recently shown that the adeno-associated virus type 2 P5 promoter +1 region (P5 + 1 element) binds transcription factor YY1 (ref. 5). (princeton.edu)
  • From 2002 to 2012, type 1 and type 2 diabetes incidence increased 1.4% and 7.1%, respectively, among U.S. youths (4). (cdc.gov)
  • The incidence of both type 1 and type 2 diabetes in U.S. youths continued to rise at constant rates throughout this period. (cdc.gov)
  • For both type 1 and type 2 diabetes, the rates of increase were generally higher among racial/ethnic minority populations than those among whites. (cdc.gov)