Bptf maintains chromatin accessibility and the self-renewal capacity of mammary gland stem cells [ChIP-Seq]

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 epithelial cells in the mammary gland. 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 and chemical inhibition of Bptf, suggests a role for this factor in maintaining the open chromatin landscape of cis-regulatory elements in mammary epithelial cells (MECs). Collectively, our study implicates Bptf in maintaining the unique epigenetic state of MaSCs. Overall design: FACS-sorted mammary epithelial cells and/or mammary epithelial cell line Eph4 were utilized for chromatin isolation and pulldown utilizing antibodies that recognized histone H3K27ac and c-Myc. Pulldown chromatin was purified and DNA utilized for the preparation of ChIP-seq libraries.