Journal article
Global Changes in the Mammary Epigenome Are Induced by Hormonal Cues and Coordinated by Ezh2
B Pal, T Bouras, W Shi, F Vaillant, JM Sheridan, N Fu, K Breslin, K Jiang, ME Ritchie, M Young, GJ Lindeman, GK Smyth, JE Visvader
Cell Reports | CELL PRESS | Published : 2013
Abstract
The mammary epithelium is a dynamic, highly hormone-responsive tissue. To explore chromatin modifications underlying its lineage specification and hormone responsiveness, we determined genome-wide histone methylation profiles of mammary epithelial subpopulations in different states. The marked differences in H3K27 trimethylation between subpopulations in the adult gland suggest that epithelial cell-fate decisions are orchestrated by polycomb-complex-mediated repression. Remarkably, the mammary epigenome underwent highly specific changes in different hormonal contexts, with a profound change being observed in the global H3K27me3 map of luminal cells during pregnancy. We therefore examined the..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
We are very grateful to A. Tarakovsky for providing floxed Ezh2 mice and J. Adams for critical review of the manuscript. We also thank GeneWorks for library preparation and sequencing of ChIP samples; D. Wu for help with bioinformatic analysis; E. Nolan, T. McLennan, B. Capaldo, and T. Ward for expert help; C. Clarke, K. Simpson, D. Reinberg, G. McArthur, and B. Sarcevic for reagents; and the animal, FACS, and histology facilities at WEHI. We thank C. Clarke, J. Carroll, and S. Clark for discussions. This work was supported by the Australian National Health and Medical Research Council (NHMRC) #461224, #461221, #637307, #637308, #1016701, and Australia Fellowship (to J.E.V.); NHMRC #490037 (to G.K.S.); the WEHI Genomics Fund; NHMRC IRIISS; the Victorian State Government through VCA funding of the Victorian Breast Cancer Research Consortium and Operational Infrastructure Support; and the ACRF. B.P. and T.B. were supported by NHMRC Biomedical and National Breast Cancer Foundation (Australia) Fellowships, respectively.