BPTF Maintains Chromatin Accessibility and the Self-Renewal Capacity of Mammary Gland Stem Cells.
BPTF Maintains Chromatin Accessibility and the Self-Renewal Capacity of Mammary Gland Stem Cells.
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BPTF保持染色质的可及性和乳腺干细胞的自我更新能力。
DOI：
10.1016/j.stemcr.2017.04.031
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发表时间：
2017-07-11
影响因子：
5.9
通讯作者：
Dos Santos CO
中科院分区：
文献类型：
--
作者：
Frey WD;Chaudhry A;Slepicka PF;Ouellette AM;Kirberger SE;Pomerantz WCK;Hannon GJ;Dos Santos CO
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. BPTF depletion leads to arrest of mammary gland development BPTF KO MaSCs fail to self-renew and differentiate BPTF KO alters chromatin accessibility and gene expression regulation of MECs Chemical BPTF inhibition changes the growth and survival of MECs In this article, dos Santos and colleagues show that BPTF-dependent chromatin remodeling is essential for mammary gland development and MaSC self-renewal. Alterations to the enhancer landscape of BPTF-depleted MaSCs resulted in differentiation arrest of uncharacterized MECs, and deregulation of genes controlling cell growth and survival. These changes demonstrate the role of chromatin organization on expression control, differentiation, and survival of MECs.
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