Poster Presentation 25th Lorne Cancer Conference 2013

Epigenomes of mouse mammary epithelial subsets (#302)

Bhupinder Pal 1 , Toula Bouras 1 , Wei Shi 1 , Francois Vaillant 1 , Julie Sheridan 1 , Naiyang Fu 1 , Kelsey Breslin 1 , Kun Jiang 1 , Matthew Young 1 , Matthew E Ritchie 1 , Geoffrey J Lindeman 1 , Gordon K Smyth 1 , Jane E Visvader 1
  1. Walter and Eliza Hall Institute of Medical Research, Parkville, Vic, Australia

The mammary epithelium is made up of two major cellular compartments consisting of basal and luminal cells. During different developmental stages including pregnancy the cellular composition of mammary epithelium is influenced by hormones. To explore the chromatin modifications underlying self-renewal, lineage commitment and differentiation along the cellular hierarchy and hormone responsiveness, we determined genome-wide histone methylation profiles of mammary epithelial subpopulations: stem cell-enriched, luminal progenitor and mature luminal cells under virgin and pregnancy conditions. Each subpopulation was found to have a unique H3K27-trimethylation landscape, which suggests that epithelial cell-fate decisions are regulated by polycomb complex-mediated repression. In addition, the mammary epigenome underwent profound changes in the global H3K27me3 map of luminal cells during pregnancy. We therefore examined the role of the key H3K27 methyltransferase Ezh2 in mammary physiology. Our findings reveal that Ezh2 couples hormonal stimuli to epigenetic changes that drive alveolar expansion in the mammary gland.