These authors contributed equally to this work. The nuclear factor CREB stimulates the expression of cellular genes following its protein kinase A-mediated phosphorylation at Ser-133. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error, CREB mediates a broad transcriptional response to cAMP in pancreatic beta cells. Effect of ACREB is indicated. Ubiquitous CREB target genes are induced following recruitment of CREB and its coactivators to promoter proximal binding sites. (B) Heat map depicting CREB occupancy restricted to activated genomic regions (H3AcK27-decorated promoters and enhancers) that are tissue specific or shared between islets and hepatocytes. (A) Motif analysis of tissue-specific…, Neurod1 promotes CREB occupancy at binding sites within beta cell-specific enhancers. Ser-133 phosphorylation, in turn, activates target gene expression by promoting recruitment of the co-activator CBP. USA.gov. for example, leads to a defect in spermatogenesis secondary to germ cell apoptosis (17,18). CREB target genes are a core component of the TTP-low tumor gene signature. In order to characterize CREB target genes in various tissues, we give a cAMP agonist, forskolin (FSK), to cell lines or primary cultures and monitor the gene expression.
phosphorylation of phospho(Ser-133) CREB at Ser-142 strongly inhibits target gene activation (14). Copyright © 2019 American Society for Microbiology.
↵* The costs of publication of this article were defrayed in part by the payment of page charges. CBP/p300 double null cells reveal effect of coactivator level and diversity on CREB transactivation. In an effort to seek novel CREB-responsive target genes associated with the G1/S progression in AML cells, we analyzed a previous microarray dataset for CREB knockdown K562 chronic myeloid leukemia cells (Gene Expression Omnibus (GEO) accession GDS3487). We found that CREB stimulates the expression of pancreatic beta cell-specific genes by targeting CBP/p300 to promoter-distal enhancer regions. Section 1734 solely to indicate this fact. Recent studies indicate that CREB functions importantly in promoting cell survival. All rights reserved. Regulation of somatostatin gene transcription by cyclic adenosine monophosphate. (C) Effect of RNAi-mediated depletion of Neurod1 on induction of core (, Neurod1 promotes CREB occupancy at binding sites within beta cell-specific enhancers. Target validation experiments revealed a core promoter requirement for transcriptional induction via CREB; TATA-less promoters were unresponsive to cAMP compared to TATA-containing genes, despite comparable binding of CREB to both sets of genes in vivo. Get the latest public health information from CDC: https://www.coronavirus.gov. These results illustrate a mechanism by which subsets of target genes for a transcription factor are differentially regulated depending on core promoter configuration. The majority of tissue-restricted CREB occupancy occurs in TSS-distal genomic loci (promoter-TSS, −1,000/+100 bp from TSS).
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