The BET family member BRD4 interacts with OCT4 and regulates pluripotency gene expression

Tao Wu; Hugo Borges Pinto; Yasunao F. Kamikawa; Mary E. Donohoe

doi:10.1016/j.stemcr.2015.01.012

The BET family member BRD4 interacts with OCT4 and regulates pluripotency gene expression

Tao Wu, Hugo Borges Pinto, Yasunao F. Kamikawa, Mary E. Donohoe

Research output: Contribution to journal › Article › peer-review

67 Scopus citations

Abstract

Embryonic stem cell (ESC) pluripotency is controlled by defined transcription factors. During cellular differentiation, ESCs undergo a global epigenetic reprogramming. Female ESCs exemplify this process as one of the two X-chromosomes is globally silenced during X chromosome inactivation (XCI) to balance the X-linked gene disparity with XY males. The pluripotent factor OCT4 regulates XCI by triggering X chromosome pairing and counting. OCT4 directly binds Xite and Tsix, which encode two long noncoding RNAs (lncRNAs) that suppress the silencer lncRNA, Xist. To control its activity as a master regulator in pluripotency and XCI, OCT4 must have chromatin protein partners. Here we show that BRD4, a member of the BET protein subfamily, interacts with OCT4. BRD4 occupies the regulatory regions of pluripotent genes and the lncRNAs of XCI. BET inhibition or depletion of BRD4 reduces the expression of many pluripotent genes and shifts cellular fate showing that BRD4 is pivotal for transcription in ESCs.

Original language	English (US)
Pages (from-to)	390-403
Number of pages	14
Journal	Stem Cell Reports
Volume	4
Issue number	3
DOIs	https://doi.org/10.1016/j.stemcr.2015.01.012
State	Published - Mar 10 2015
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Genetics
Developmental Biology
Cell Biology

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title = "The BET family member BRD4 interacts with OCT4 and regulates pluripotency gene expression",

abstract = "Embryonic stem cell (ESC) pluripotency is controlled by defined transcription factors. During cellular differentiation, ESCs undergo a global epigenetic reprogramming. Female ESCs exemplify this process as one of the two X-chromosomes is globally silenced during X chromosome inactivation (XCI) to balance the X-linked gene disparity with XY males. The pluripotent factor OCT4 regulates XCI by triggering X chromosome pairing and counting. OCT4 directly binds Xite and Tsix, which encode two long noncoding RNAs (lncRNAs) that suppress the silencer lncRNA, Xist. To control its activity as a master regulator in pluripotency and XCI, OCT4 must have chromatin protein partners. Here we show that BRD4, a member of the BET protein subfamily, interacts with OCT4. BRD4 occupies the regulatory regions of pluripotent genes and the lncRNAs of XCI. BET inhibition or depletion of BRD4 reduces the expression of many pluripotent genes and shifts cellular fate showing that BRD4 is pivotal for transcription in ESCs.",

author = "Tao Wu and Pinto, {Hugo Borges} and Kamikawa, {Yasunao F.} and Donohoe, {Mary E.}",

note = "Publisher Copyright: {\textcopyright} 2015 The Authors.",

year = "2015",

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doi = "10.1016/j.stemcr.2015.01.012",

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T1 - The BET family member BRD4 interacts with OCT4 and regulates pluripotency gene expression

AU - Wu, Tao

AU - Pinto, Hugo Borges

AU - Kamikawa, Yasunao F.

AU - Donohoe, Mary E.

PY - 2015/3/10

Y1 - 2015/3/10

N2 - Embryonic stem cell (ESC) pluripotency is controlled by defined transcription factors. During cellular differentiation, ESCs undergo a global epigenetic reprogramming. Female ESCs exemplify this process as one of the two X-chromosomes is globally silenced during X chromosome inactivation (XCI) to balance the X-linked gene disparity with XY males. The pluripotent factor OCT4 regulates XCI by triggering X chromosome pairing and counting. OCT4 directly binds Xite and Tsix, which encode two long noncoding RNAs (lncRNAs) that suppress the silencer lncRNA, Xist. To control its activity as a master regulator in pluripotency and XCI, OCT4 must have chromatin protein partners. Here we show that BRD4, a member of the BET protein subfamily, interacts with OCT4. BRD4 occupies the regulatory regions of pluripotent genes and the lncRNAs of XCI. BET inhibition or depletion of BRD4 reduces the expression of many pluripotent genes and shifts cellular fate showing that BRD4 is pivotal for transcription in ESCs.

AB - Embryonic stem cell (ESC) pluripotency is controlled by defined transcription factors. During cellular differentiation, ESCs undergo a global epigenetic reprogramming. Female ESCs exemplify this process as one of the two X-chromosomes is globally silenced during X chromosome inactivation (XCI) to balance the X-linked gene disparity with XY males. The pluripotent factor OCT4 regulates XCI by triggering X chromosome pairing and counting. OCT4 directly binds Xite and Tsix, which encode two long noncoding RNAs (lncRNAs) that suppress the silencer lncRNA, Xist. To control its activity as a master regulator in pluripotency and XCI, OCT4 must have chromatin protein partners. Here we show that BRD4, a member of the BET protein subfamily, interacts with OCT4. BRD4 occupies the regulatory regions of pluripotent genes and the lncRNAs of XCI. BET inhibition or depletion of BRD4 reduces the expression of many pluripotent genes and shifts cellular fate showing that BRD4 is pivotal for transcription in ESCs.

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The BET family member BRD4 interacts with OCT4 and regulates pluripotency gene expression

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