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Nat Commun. 2015 Feb 18;6:6351. doi: 10.1038/ncomms7351.

Epigenetic and transcriptional determinants of the human breast.

Author information

1
Department of Pathology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94143, USA.
2
Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3.
3
Centre for High-Throughput Biology and Department of Microbiology &Immunology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
4
Department of Neurological Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94143, USA.
5
The Genome Center, University of California-Davis, Davis, California 95616, USA.
6
Department of Microbiology and Immunology, UCSF Diabetes Center, Department of Medicine, University of California San Francisco, San Francisco, California 94143, USA.
7
Department of Dermatology, University of California San Francisco, San Francisco, California 94143, USA.
8
Department of Medicine, Institute for Human Genetics and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94115, USA.
9
School of Medicine, Department of Genetics, Washington University in St Louis, St Louis, Missouri 63108, USA.
10
Department of Biochemistry &Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90033, USA.
11
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.
12
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.

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.

PMID:
25690954
PMCID:
PMC4346612
DOI:
10.1038/ncomms7351
[Indexed for MEDLINE]
Free PMC Article

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