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| Status |
Public on Mar 26, 2019 |
| Title |
TCF21 and AP-1 interact through epigenetic modifications to regulate coronary artery disease gene expression [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The majority of genetic variation associated with coronary artery disease (CAD) resides in non- coding regions that are expected to involve transcriptional and epigenetic mechanisms of gene expression. We have identified a transcriptional network downstream of the CAD associated transcription factor (TF) TCF21 and provide evidence for TCF21 colocalization and co- regulation with the activator protein-1 (AP-1) complex in disease loci. We show that TCF21 and AP-1 regulate expression of two causal CAD genes, SMAD3 and CDKN2B-AS1, in part by interactions with histone acetyltransferases and deacetylases. Genome-wide, TCF21 and AP-1 are jointly localized, regulate chromatin accessibility, and are enriched in CAD loci. These data show that the known chromatin remodeling and pioneer functions of AP-1 are a pervasive aspect of epigenetic control of transcription and thus risk in CAD associated loci, and that interaction of AP-1 with TCF21 to control epigenetic features contributes to the genetic risk in loci where they colocalize.
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| Overall design |
Human coronary artery smooth muscle cells (HCASMC) grown in serum were evaluated with an antibody to H3K27ac, or input control with siRNA of JUN, shRNA of TCF21 or control knockdown.
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| Contributor(s) |
Zhao Q, Wirka R, Nguyen T, Nagao M, Cheng P, Miller CL, Kim JB, Pjanic M, Quertermous T |
| Citation(s) |
31014396 |
| |
| Submission date |
Nov 20, 2018 |
| Last update date |
May 09, 2019 |
| Contact name |
Thomas Quertermous |
| E-mail(s) |
[email protected]
|
| Phone |
650-723-5012
|
| Organization name |
Stanford University
|
| Department |
Medicine Cardiology
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| Lab |
Quertermous
|
| Street address |
300 Pasteur Drive
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| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
94305 |
| Country |
USA |
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| Platforms (1) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE122758 |
TCF21 and AP-1 interact through epigenetic modifications to regulate coronary artery disease gene expression |
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| Relations |
| BioProject |
PRJNA506320 |
| SRA |
SRP170064 |
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