title: Epigenetic and transcriptional determinants of the human breast.
abstract: While significant effort has been dedicated to the characterization of epigenetic changes associated with prenatal differentiation, relatively little is known about the epigenetic changes that accompany post-natal differentiation where fully functional differentiated cell types with limited lifespans arise. Here we sought to address this gap by generating epigenomic and transcriptional profiles from primary human breast cell types isolated from disease-free human subjects. From these data we define a comprehensive human breast transcriptional network, including a set of myoepithelial- and luminal epithelial-specific intronic retention events. Intersection of epigenetic states with RNA expression from distinct breast epithelium lineages demonstrates that mCpG provides a stable record of exonic and intronic usage, whereas H3K36me3 is dynamic. We find a striking asymmetry in epigenomic reprogramming between luminal and myoepithelial cell types, with the genomes of luminal cells harbouring more than twice the number of hypomethylated enhancer elements compared with myoepithelial cells.
authors.affiliation: Department of Pathology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94143, USA.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gascard
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3.
authors.forename: Misha
authors.initials: M
authors.lastname: Bilenky
authors.affiliation: Department of Pathology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94143, USA.
authors.forename: Mahvash
authors.initials: M
authors.lastname: Sigaroudinia
authors.affiliation: Department of Pathology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94143, USA.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Centre for High-Throughput Biology and Department of Microbiology &Immunology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
authors.forename: Luolan
authors.initials: L
authors.lastname: Li
authors.affiliation: Centre for High-Throughput Biology and Department of Microbiology &Immunology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
authors.forename: Annaick
authors.initials: A
authors.lastname: Carles
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3.
authors.forename: Allen
authors.initials: A
authors.lastname: Delaney
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3.
authors.forename: Angela
authors.initials: A
authors.lastname: Tam
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3.
authors.forename: Baljit
authors.initials: B
authors.lastname: Kamoh
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Cho
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3.
authors.forename: Malachi
authors.initials: M
authors.lastname: Griffith
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3.
authors.forename: Andy
authors.initials: A
authors.lastname: Chu
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3.
authors.forename: Gordon
authors.initials: G
authors.lastname: Robertson
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Cheung
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3.
authors.forename: Irene
authors.initials: I
authors.lastname: Li
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3.
authors.forename: Alireza
authors.initials: A
authors.lastname: Heravi-Moussavi
authors.affiliation: Centre for High-Throughput Biology and Department of Microbiology &Immunology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
authors.forename: Michelle
authors.initials: M
authors.lastname: Moksa
authors.affiliation: Centre for High-Throughput Biology and Department of Microbiology &Immunology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
authors.forename: Matthew
authors.initials: M
authors.lastname: Mingay
authors.affiliation: Centre for High-Throughput Biology and Department of Microbiology &Immunology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
authors.forename: Angela
authors.initials: A
authors.lastname: Hussainkhel
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3.
authors.forename: Brad
authors.initials: B
authors.lastname: Davis
authors.affiliation: Department of Neurological Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94143, USA.
authors.forename: Raman P
authors.initials: RP
authors.lastname: Nagarajan
authors.affiliation: Department of Neurological Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94143, USA.
authors.forename: Chibo
authors.initials: C
authors.lastname: Hong
authors.affiliation: The Genome Center, University of California-Davis, Davis, California 95616, USA.
authors.forename: Lorigail
authors.initials: L
authors.lastname: Echipare
authors.affiliation: The Genome Center, University of California-Davis, Davis, California 95616, USA.
authors.forename: Henriette
authors.initials: H
authors.lastname: O'Geen
authors.affiliation: Department of Microbiology and Immunology, UCSF Diabetes Center, Department of Medicine, University of California San Francisco, San Francisco, California 94143, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Hangauer
authors.affiliation: Department of Dermatology, University of California San Francisco, San Francisco, California 94143, USA.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Cheng
authors.affiliation: Department of Neurological Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94143, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Neel
authors.affiliation: Department of Medicine, Institute for Human Genetics and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94115, USA.
authors.forename: Donglei
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Microbiology and Immunology, UCSF Diabetes Center, Department of Medicine, University of California San Francisco, San Francisco, California 94143, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: McManus
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3.
authors.forename: Richard
authors.initials: R
authors.lastname: Moore
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mungall
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3.
authors.forename: Yussanne
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3.
authors.forename: Patrick
authors.initials: P
authors.lastname: Plettner
authors.affiliation: Department of Medicine, Institute for Human Genetics and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94115, USA.
authors.forename: Elad
authors.initials: E
authors.lastname: Ziv
authors.affiliation: School of Medicine, Department of Genetics, Washington University in St Louis, St Louis, Missouri 63108, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Biochemistry &Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90033, USA.
authors.forename: Peggy J
authors.initials: PJ
authors.lastname: Farnham
authors.affiliation: 1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3 [2] Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada V6H 3N1.
authors.forename: Steven J M
authors.initials: SJ
authors.lastname: Jones
authors.affiliation: 1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3 [2] Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada V6H 3N1.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Marra
authors.affiliation: Department of Pathology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94143, USA.
authors.forename: Thea D
authors.initials: TD
authors.lastname: Tlsty
authors.affiliation: Department of Neurological Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94143, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Costello
authors.affiliation: 1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3 [2] Centre for High-Throughput Biology and Department of Microbiology &Immunology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
authors.forename: Martin
authors.initials: M
authors.lastname: Hirst
mesh_terms: D001940:Breast / Q000166:cytology / Q000378:metabolism*; D002453:Cell Cycle; D002454:Cell Differentiation; D002469:Cell Separation; D002843:Chromatin / Q000737:chemistry; D047369:Chromatin Immunoprecipitation; D018899:CpG Islands; D044127:Epigenesis, Genetic; D057890:Epigenomics; D004847:Epithelial Cells / Q000166:cytology; D005091:Exons; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D015894:Genome, Human; D006657:Histones / Q000737:chemistry; D006801:Humans; D007438:Introns; D007621:Karyotyping; D035683:MicroRNAs / Q000378:metabolism; D017423:Sequence Analysis, RNA; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D006657:Histones; D035683:MicroRNAs