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Series GSE126557 Query DataSets for GSE126557
Status Public on Jun 16, 2019
Title CREB mediates transient and sustained genomic responses to cAMP via distinct mechanisms [RNA-seq]
Organisms Mus musculus; Rattus norvegicus
Experiment type Expression profiling by high throughput sequencing
Summary We investigated genome-wide occupancy of CREB, CREB coactivators, lineage determining transcription factors and histone acetylation to uncover mechanisms behind tissue-specific gene induction by cAMP in pancreatic islets. CREB mediates effects of cAMP on cellular gene expression. Most core CREB target genes are ubiquitously induced following recruitment of CREB and its coactivators to promoter proximal binding sites. We found that CREB stimulates the expression of pancreatic beta cell genes by binding to sites within distal enhancers. By contrast with its transient effects on core target genes, CREB stimulates pancreatic beta cell specific gene expression in a sustained manner, reflecting increases in the CBP-mediated acetylation of resident nucleosomes that recruit the chromatin reader BRD4. CREB cooperates with the lineage specific activator Neurod1 in establishing cAMP-responsive enhancers in beta cells. As deletion of a CREB-Neurod1 bound enhancer within the Lrrc10b-Syt7 super-enhancer locus disrupted the expression of both genes and decreased glucose-induced insulin secretion, our results demonstrate how cooperativity between signal dependent and lineage determining factors promotes the expression of cell type-specific gene programs in response to extracellular cues.
Overall design RNA-seq was performed in primary mouse islets and hepatocytes as well as rat pancreatic cell lines.
Contributor(s) Van de Velde S
Citation(s) 31182641
Submission date Feb 14, 2019
Last update date Jun 16, 2019
Contact name Sam Van de Velde
Organization name Salk Institute
Department PBL
Street address 10010 North Torrey Pines Road
City La Jolla
State/province CA
ZIP/Postal code 92037
Country USA
Platforms (2)
GPL16417 Illumina MiSeq (Mus musculus)
GPL19052 Illumina MiSeq (Rattus norvegicus)
Samples (22)
GSM3604512 isletCON_rep1 [RNA-seq]
GSM3604513 isletFSK_rep1 [RNA-seq]
GSM3604514 isletCON_rep2 [RNA-seq]
This SubSeries is part of SuperSeries:
GSE126558 CREB mediates transient and sustained genomic responses to cAMP via distinct mechanisms
BioProject PRJNA522365
SRA SRP185890

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Supplementary file Size Download File type/resource
GSE126557_AR42JGFPvNeuroD1RNAseq.xlsx 810.0 Kb (ftp)(http) XLSX
GSE126557_INS1JQ1A485FSKRNAseq.xlsx 814.2 Kb (ftp)(http) XLSX
GSE126557_INS1RNAseqrepeat.xlsx 2.8 Mb (ftp)(http) XLSX
GSE126557_WTvCRTC2KOisletRNAseq.xlsx 1.0 Mb (ftp)(http) XLSX
GSE126557_mousehepaRNAseqrepeat.xlsx 3.9 Mb (ftp)(http) XLSX
GSE126557_mouseisletRNAseqrepeats.xlsx 4.2 Mb (ftp)(http) XLSX
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Processed data are available on Series record

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