title: Epigenetic regulation of cell type-specific expression patterns in the human mammary epithelium.
abstract: Differentiation is an epigenetic program that involves the gradual loss of pluripotency and acquisition of cell type-specific features. Understanding these processes requires genome-wide analysis of epigenetic and gene expression profiles, which have been challenging in primary tissue samples due to limited numbers of cells available. Here we describe the application of high-throughput sequencing technology for profiling histone and DNA methylation, as well as gene expression patterns of normal human mammary progenitor-enriched and luminal lineage-committed cells. We observed significant differences in histone H3 lysine 27 tri-methylation (H3K27me3) enrichment and DNA methylation of genes expressed in a cell type-specific manner, suggesting their regulation by epigenetic mechanisms and a dynamic interplay between the two processes that together define developmental potential. The technologies we developed and the epigenetically regulated genes we identified will accelerate the characterization of primary cell epigenomes and the dissection of human mammary epithelial lineage-commitment and luminal differentiation.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: Reo
authors.initials: R
authors.lastname: Maruyama
authors.forename: Sibgat
authors.initials: S
authors.lastname: Choudhury
authors.forename: Adam
authors.initials: A
authors.lastname: Kowalczyk
authors.forename: Marina
authors.initials: M
authors.lastname: Bessarabova
authors.forename: Bryan
authors.initials: B
authors.lastname: Beresford-Smith
authors.forename: Thomas
authors.initials: T
authors.lastname: Conway
authors.forename: Antony
authors.initials: A
authors.lastname: Kaspi
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Wu
authors.forename: Tatiana
authors.initials: T
authors.lastname: Nikolskaya
authors.forename: Vanessa F
authors.initials: VF
authors.lastname: Merino
authors.forename: Pang-Kuo
authors.initials: PK
authors.lastname: Lo
authors.forename: X Shirley
authors.initials: XS
authors.lastname: Liu
authors.forename: Yuri
authors.initials: Y
authors.lastname: Nikolsky
authors.forename: Saraswati
authors.initials: S
authors.lastname: Sukumar
authors.forename: Izhak
authors.initials: I
authors.lastname: Haviv
authors.forename: Kornelia
authors.initials: K
authors.lastname: Polyak
mesh_terms: D051927:CD24 Antigen / Q000235:genetics; D002454:Cell Differentiation; D002843:Chromatin / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics; D042361:Mammary Glands, Human / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D014157:Transcription Factors / Q000235:genetics
chemical_list: D051927:CD24 Antigen; C497889:CD24 protein, human; C497483:CD44 protein, human; D002843:Chromatin; D006657:Histones; D018960:Hyaluronan Receptors; D014157:Transcription Factors