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

Research output: Contribution to journalArticle

14 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 languageEnglish (US)
Pages (from-to)23-31
Number of pages9
JournalStem Cell Reports
Volume9
Issue number1
DOIs
StatePublished - Jul 11 2017

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Keywords

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

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