BPTF Maintains Chromatin Accessibility and the Self-Renewal Capacity of Mammary Gland Stem Cells

Wesley D. Frey; Anisha Chaudhry; Priscila F. Slepicka; Adam M. Ouellette; Steven E. Kirberger; William C.K. Pomerantz; Gregory J. Hannon; Camila O. dos Santos

doi:10.1016/j.stemcr.2017.04.031

BPTF Maintains Chromatin Accessibility and the Self-Renewal Capacity of Mammary Gland Stem Cells

Wesley D. Frey, Anisha Chaudhry, Priscila F. Slepicka, Adam M. Ouellette, Steven E. Kirberger, William C.K. Pomerantz, Gregory J. Hannon, Camila O. dos Santos

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40 Scopus citations

Abstract

Chromatin remodeling is a key requirement for transcriptional control of cellular differentiation. However, the factors that alter chromatin architecture in mammary stem cells (MaSCs) are poorly understood. Here, we show that BPTF, the largest subunit of the NURF chromatin remodeling complex, is essential for MaSC self-renewal and differentiation of mammary epithelial cells (MECs). BPTF depletion arrests cells at a previously undefined stage of epithelial differentiation that is associated with an incapacity to achieve the luminal cell fate. Moreover, genome-wide analysis of DNA accessibility following genetic or chemical inhibition, suggests a role for BPTF in maintaining the open chromatin landscape at enhancers regions in MECs. Collectively, our study implicates BPTF in maintaining the unique epigenetic state of MaSCs.

Original language	English (US)
Pages (from-to)	23-31
Number of pages	9
Journal	Stem Cell Reports
Volume	9
Issue number	1
DOIs	https://doi.org/10.1016/j.stemcr.2017.04.031
State	Published - Jul 11 2017
Externally published	Yes

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Publisher Copyright:
© 2017 The Author(s)

Keywords

BPTF
chromatin remodeling
enhancer landscape
gene regulation
mammary gland development
mammary stem cells

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "BPTF Maintains Chromatin Accessibility and the Self-Renewal Capacity of Mammary Gland Stem Cells",

abstract = "Chromatin remodeling is a key requirement for transcriptional control of cellular differentiation. However, the factors that alter chromatin architecture in mammary stem cells (MaSCs) are poorly understood. Here, we show that BPTF, the largest subunit of the NURF chromatin remodeling complex, is essential for MaSC self-renewal and differentiation of mammary epithelial cells (MECs). BPTF depletion arrests cells at a previously undefined stage of epithelial differentiation that is associated with an incapacity to achieve the luminal cell fate. Moreover, genome-wide analysis of DNA accessibility following genetic or chemical inhibition, suggests a role for BPTF in maintaining the open chromatin landscape at enhancers regions in MECs. Collectively, our study implicates BPTF in maintaining the unique epigenetic state of MaSCs.",

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AU - Frey, Wesley D.

AU - Chaudhry, Anisha

AU - Slepicka, Priscila F.

AU - Ouellette, Adam M.

AU - Kirberger, Steven E.

AU - Pomerantz, William C.K.

AU - Hannon, Gregory J.

AU - dos Santos, Camila O.

PY - 2017/7/11

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N2 - Chromatin remodeling is a key requirement for transcriptional control of cellular differentiation. However, the factors that alter chromatin architecture in mammary stem cells (MaSCs) are poorly understood. Here, we show that BPTF, the largest subunit of the NURF chromatin remodeling complex, is essential for MaSC self-renewal and differentiation of mammary epithelial cells (MECs). BPTF depletion arrests cells at a previously undefined stage of epithelial differentiation that is associated with an incapacity to achieve the luminal cell fate. Moreover, genome-wide analysis of DNA accessibility following genetic or chemical inhibition, suggests a role for BPTF in maintaining the open chromatin landscape at enhancers regions in MECs. Collectively, our study implicates BPTF in maintaining the unique epigenetic state of MaSCs.

AB - Chromatin remodeling is a key requirement for transcriptional control of cellular differentiation. However, the factors that alter chromatin architecture in mammary stem cells (MaSCs) are poorly understood. Here, we show that BPTF, the largest subunit of the NURF chromatin remodeling complex, is essential for MaSC self-renewal and differentiation of mammary epithelial cells (MECs). BPTF depletion arrests cells at a previously undefined stage of epithelial differentiation that is associated with an incapacity to achieve the luminal cell fate. Moreover, genome-wide analysis of DNA accessibility following genetic or chemical inhibition, suggests a role for BPTF in maintaining the open chromatin landscape at enhancers regions in MECs. Collectively, our study implicates BPTF in maintaining the unique epigenetic state of MaSCs.

KW - BPTF

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KW - enhancer landscape

KW - gene regulation

KW - mammary gland development

KW - mammary stem cells

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BPTF Maintains Chromatin Accessibility and the Self-Renewal Capacity of Mammary Gland Stem Cells

Abstract

Bibliographical note

Keywords

UN SDGs

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