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Enhancer Decommissioning by LSD1 During Embryonic Stem Cell Differentiation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE27844 | GEO | 2012/01/03

SECONDARY ACCESSION(S): PRJNA138041

REPOSITORIES: GEO

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Enhancer decommissioning by LSD1 during embryonic stem cell differentiation.

Project description:Transcription factors and chromatin modifiers are important in the programming and reprogramming of cellular states during development. Transcription factors bind to enhancer elements and recruit coactivators and chromatin-modifying enzymes to facilitate transcription initiation. During differentiation a subset of these enhancers must be silenced, but the mechanisms underlying enhancer silencing are poorly understood. Here we show that the histone demethylase lysine-specific demethylase 1 (LSD1; ref. 5), which demethylates histone H3 on Lys?4 or Lys?9 (H3K4/K9), is essential in decommissioning enhancers during the differentiation of mouse embryonic stem cells (ESCs). LSD1 occupies enhancers of active genes that are critical for control of the state of ESCs. However, LSD1 is not essential for the maintenance of ESC identity. Instead, ESCs lacking LSD1 activity fail to differentiate fully, and ESC-specific enhancers fail to undergo the histone demethylation events associated with differentiation. At active enhancers, LSD1 is a component of the NuRD (nucleosome remodelling and histone deacetylase) complex, which contains additional subunits that are necessary for ESC differentiation. We propose that the LSD1-NuRD complex decommissions enhancers of the pluripotency program during differentiation, which is essential for the complete shutdown of the ESC gene expression program and the transition to new cell states.

| S-EPMC4144424 | biostudies-literature

Enhancer Decommissioning by LSD1 During Embryonic Stem Cell Differentiation

Project description:This SuperSeries is composed of the following subset Series: GSE27714: Enhancer Decommissioning by LSD1 During Embryonic Stem Cell Differentiation (expression) GSE27841: Enhancer Decommissioning by LSD1 During Embryonic Stem Cell Differentiation (ChIP-seq) Refer to individual Series

2012-01-03 | E-GEOD-27844 | biostudies-arrayexpress

Enhancer Decommissioning by LSD1 During Embryonic Stem Cell Differentiation (expression)

Project description:Transcription factors and chromatin modifiers play important roles in programming and reprogramming of cellular states during development. Much is known about the role of these regulators in gene activation, but relatively little is known about the critical process of enhancer silencing during differentiation. Here we show that the H3K4/K9 histone demethylase LSD1 plays an essential role in decommissioning enhancers during differentiation of embryonic stem cells (ESCs). LSD1 occupies enhancers of active genes critical for control of ESC state. However, LSD1 is not essential for maintenance of ESC identity. Instead, ESCs lacking LSD1 activity fail to fully differentiate and ESC-specific enhancers fail to undergo the histone demethylation events associated with differentiation. At enhancers, LSD1 is a component of the NuRD complex, which contains additional subunits that are necessary for ESC differentiation. We propose that the LSD1-NuRD complex decommissions enhancers of the pluripotency program upon differentiation, which is essential for complete shutdown of the ESC gene expression program and the transition to new cell states. This represents the expression part of the study.

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Enhancer Decommissioning by LSD1 During Embryonic Stem Cell Differentiation (ChIP-seq)

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Enhancer Decommissioning by LSD1 During Embryonic Stem Cell Differentiation (expression)

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Enhancer Decommissioning by LSD1 During Embryonic Stem Cell Differentiation (ChIP-seq)

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Foxd3 promotes the exit from naïve pluripotency and prevents germline specification through enhancer decommissioning

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series