Genomics

Dataset Information

154

A UTX–MLL4–p300 Transcriptional Regulatory Network Coordinately Shapes Active Enhancer Landscapes for Eliciting Transcription (ChIP-Seq)


ABSTRACT: 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. Overall design: ChIP-sequencing of mouse ES cells.

INSTRUMENT(S): Illumina HiSeq 2000 (Mus musculus)

SUBMITTER: Richard Koche  

PROVIDER: GSE97701 | GEO | 2017-07-06

SECONDARY ACCESSION(S): PRJNA382688

REPOSITORIES: GEO

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Publications

A UTX-MLL4-p300 Transcriptional Regulatory Network Coordinately Shapes Active Enhancer Landscapes for Eliciting Transcription.

Wang Shu-Ping SP   Tang Zhanyun Z   Chen Chun-Wei CW   Shimada Miho M   Koche Richard P RP   Wang Lan-Hsin LH   Nakadai Tomoyoshi T   Chramiec Alan A   Krivtsov Andrei V AV   Armstrong Scott A SA   Roeder Robert G RG  

Molecular cell 20170701 2


Enhancer activation is a critical step for gene activation. Here we report an 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 inactive 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 atten  ...[more]

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