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.
authors.affiliation: Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Davide
authors.initials: D
authors.lastname: Pellacani
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Misha
authors.initials: M
authors.lastname: Bilenky
authors.affiliation: Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Nagarajan
authors.initials: N
authors.lastname: Kannan
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Alireza
authors.initials: A
authors.lastname: Heravi-Moussavi
authors.affiliation: Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: David J H F
authors.initials: DJHF
authors.lastname: Knapp
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Sitanshu
authors.initials: S
authors.lastname: Gakkhar
authors.affiliation: Michael Smith Laboratories, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Moksa
authors.affiliation: Michael Smith Laboratories, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
authors.forename: Annaick
authors.initials: A
authors.lastname: Carles
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Moore
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mungall
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Marra
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Steven J M
authors.initials: SJM
authors.lastname: Jones
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
authors.forename: Samuel
authors.initials: S
authors.lastname: Aparicio
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada; Michael Smith Laboratories, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada. Electronic address: mhirst@bcgsc.ca.
authors.forename: Martin
authors.initials: M
authors.lastname: Hirst
authors.affiliation: Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada. Electronic address: ceaves@bccrc.ca.
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Eaves
mesh_terms: D000328:Adult; D001940:Breast / Q000378:metabolism*; D002469:Cell Separation; D002843:Chromatin / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D044127:Epigenesis, Genetic; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D053263:Gene Regulatory Networks; D006801:Humans; D010641:Phenotype; D011401:Promoter Regions, Genetic; D015203:Reproducibility of Results; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D002843:Chromatin; D014157:Transcription Factors
keywords: chromatin; enhancer; epigenomic; mammary cells; normal human breast; profiling; regulatory network; stem cells; transcription factors; transcriptome