@article{2ee665e917c84f069f2185dab24cd87e,
title = "Analysis of Normal Human Mammary Epigenomes Reveals Cell-Specific Active Enhancer States and Associated Transcription Factor Networks",
abstract = "The normal adult human mammary gland is a continuous bilayered epithelial system. Bipotent and myoepithelial progenitors are prominent and unique components of the outer (basal) layer. The inner (luminal) layer includes both luminal-restricted progenitors and a phenotypically separable fraction that lacks progenitor activity. We now report an epigenomic comparison of these three subsets with one another, with their associated stromal cells, and with three immortalized, non-tumorigenic human mammary cell lines. Each genome-wide analysis contains profiles for six histone marks, methylated DNA, and RNA transcripts. Analysis of these datasets shows that each cell type has unique features, primarily within genomic regulatory regions, and that the cell lines group together. Analyses of the promoter and enhancer profiles place the luminal progenitors in between the basal cells and the non-progenitor luminal subset. Integrative analysis reveals networks of subset-specific transcription factors.",
keywords = "chromatin, enhancer, epigenomic, mammary cells, normal human breast, profiling, regulatory network, stem cells, transcription factors, transcriptome",
author = "Davide Pellacani and Misha Bilenky and Nagarajan Kannan and Alireza Heravi-Moussavi and Knapp, {David J.H.F.} and Sitanshu Gakkhar and Michelle Moksa and Annaick Carles and Richard Moore and Mungall, {Andrew J.} and Marra, {Marco A.} and Jones, {Steven J.M.} and Samuel Aparicio and Martin Hirst and Eaves, {Connie J.}",
note = "Funding Information: The authors thank D. Wilkinson, G. Edin, and M. Hale for excellent technical support; Drs. E. Bovill, J. Boyle, S. Bristol, P. Gdalevitch, A. Seal, J. Sproul, and N. van Laeken for access to discarded reduction mammoplasty tissue; and E. Chun and Dr. A. Gagliardi for critical reading of this manuscript. This work was supported by the Canadian Cancer Society Research Institute (grants 702294 and 702851 ) and by Genome British Columbia and the Canadian Institutes of Health Research as part of the Canadian Epigenetics, Environment and Health Research Consortium Network ( CIHR-262119 ). N.K. was supported by a MITACS Elevate Fellowship (application ref. IT02817 ). D.J.H.F.K. received a Vanier Canada Graduate Scholarship from CIHR ( CGV-121184 ). S.A. is supported by a Canada Research Chair in Molecular Oncology. Publisher Copyright: {\textcopyright} 2016 The Author(s)",
year = "2016",
month = nov,
day = "15",
doi = "10.1016/j.celrep.2016.10.058",
language = "English (US)",
volume = "17",
pages = "2060--2074",
journal = "Cell reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "8",
}