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| Status |
Public on Jul 06, 2017 |
| Title |
A UTX–MLL4–p300 Transcriptional Regulatory Network Coordinately Shapes Active Enhancer Landscapes for Eliciting Transcription (RNA-Seq) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Enhancer activation is a critical step for gene activation. Here we report a novel epigenetic crosstalk at enhancers between the UTX (H3K27 demethylase)-MLL4 (H3K4 methyltransferase) complex and the histone acetyltransferase p300. We demonstrate that UTX, in a demethylase activity-independent manner, facilitates conversion of naïve (unmarked) enhancers in embryonic stem cells to an active (H3K4me1+/H3K27ac+) state by recruiting and coupling the enzymatic functions of MLL4 and p300. Loss of UTX leads to attenuated enhancer activity, characterized by reduced levels of H3K4me1 and H3K27ac as well as impaired transcription. The UTX-MLL4 complex enhances p300-dependent H3K27 acetylation through UTX-dependent stimulation of p300 recruitment while MLL4-mediated H3K4 monomethylation, reciprocally, requires p300 function. Importantly, MLL4-generated H3K4me1 further enhances p300-dependent transcription. This work reveals a previously unrecognized cooperativity among enhancer-associated chromatin modulators, including a unique function for UTX, in establishing an “active enhancer landscape” and defines a mechanism for the joint deposition of H3K4me1 and H3K27ac.
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| |
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| Overall design |
RNA-sequencing of mouse ES cells.
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| |
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| Contributor(s) |
Wang S, Koche RP, Roeder RG |
| Citation(s) |
28732206 |
| |
| Submission date |
Apr 12, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Richard Koche |
| E-mail(s) |
[email protected]
|
| Organization name |
Memorial Sloan Kettering Cancer Center
|
| Street address |
417 E. 68th St.
|
| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10065 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (9)
|
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| This SubSeries is part of SuperSeries: |
| GSE97703 |
A UTX–MLL4–p300 Transcriptional Regulatory Network Coordinately Shapes Active Enhancer Landscapes for Eliciting Transcription |
|
| Relations |
| BioProject |
PRJNA382689 |
| SRA |
SRP103837 |
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