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| 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.
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| Overall design |
RNA-seq was performed in primary mouse islets and hepatocytes as well as rat pancreatic cell lines.
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| 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 |
| |
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| Platforms (2) |
| GPL16417 |
Illumina MiSeq (Mus musculus) |
| GPL19052 |
Illumina MiSeq (Rattus norvegicus) |
|
| Samples (22)
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| This SubSeries is part of SuperSeries: |
| GSE126558 |
CREB mediates transient and sustained genomic responses to cAMP via distinct mechanisms |
|
| Relations |
| BioProject |
PRJNA522365 |
| SRA |
SRP185890 |
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