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| Status |
Public on May 22, 2018 |
| Title |
BRG1 governs Glucocorticoid Receptor interactions with chromatin and pioneer factors across the genome |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing Expression profiling by high throughput sequencing
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| Summary |
The Glucocorticoid Receptor (GR) alters transcriptional activity in response to hormones by interacting with chromatin at GR binding sites (GBSs) throughout the genome. Our work in human breast cancer cells identifies three classes of GBSs with distinct epigenetic characteristics and reveals that BRG1 interacts with GBSs prior to hormone exposure. The GBSs pre-occupied by BRG1 are more accessible and transcriptionally active than other GBSs. BRG1 is required for a proper and robust transcriptional hormone response and knockdown of BRG1 blocks recruitment of the pioneer factors FOXA1 and GATA3 to GBSs. Finally, GR interaction with FOXA1 and GATA3 binding sites was restricted to sites pre-bound by BRG1. These findings demonstrate that BRG1 establishes specialized chromatin environments that define multiple classes of GBS. This in turn predicts that GR and other transcriptional activators function via multiple distinct chromatin-based mechanisms to modulate the transcriptional response.
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| Overall design |
ChIP-seq and RNA-seq in A1-2 and A1A3 cells (both derived from T47D human breast cancer cells)
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| Contributor(s) |
Hoffman JA, Trotter KW, Ward JM, Archer TK |
| Citation(s) |
29792595 |
| |
| Submission date |
Mar 29, 2018 |
| Last update date |
Mar 26, 2019 |
| Contact name |
Jackson Andrew Hoffman |
| E-mail(s) |
jackson.hoffman@nih.gov
|
| Organization name |
NIEHS
|
| Department |
DIR
|
| Lab |
ESCBL
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| Street address |
111 TW Alexander Dr, Building 101 Room C432
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| City |
Research Triangle Park |
| State/province |
North Carolina |
| ZIP/Postal code |
27709 |
| Country |
USA |
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| Platforms (2) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (44)
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| Relations |
| BioProject |
PRJNA447949 |
| SRA |
SRP136702 |