Journal article
Canonical PRC2 function is essential for mammary gland development and affects chromatin compaction in mammary organoids
EM Michalak, MJG Milevskiy, RM Joyce, JF Dekkers, PR Jamieson, B Pal, CA Dawson, Y Hu, SH Orkin, WS Alexander, GJ Lindeman, GK Smyth, JE Visvader
Plos Biology | Published : 2018
Abstract
Distinct transcriptional states are maintained through organization of chromatin, resulting from the sum of numerous repressive and active histone modifications, into tightly packaged heterochromatin versus more accessible euchromatin. Polycomb repressive complex 2 (PRC2) is the main mammalian complex responsible for histone 3 lysine 27 trimethylation (H3K27me3) and is integral to chromatin organization. Using in vitro and in vivo studies, we show that deletion of Suz12, a core component of all PRC2 complexes, results in loss of H3K27me3 and H3K27 dimethylation (H3K27me2), completely blocks normal mammary gland development, and profoundly curtails progenitor activity in 3D organoid cultures...
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
National Health and Medical Research Council https://www.nhmrc.gov.au/ (grant numbers 1016701, 1024852, 1086727, 1054618, 1113577); IRIISS; Senior Principal Research Fellowships (grant numbers 1058344, 1078730, 1058892, 1102742 held by WSA, GJL, GKS, and JEV, respectively). Operational Infrastructure Support from the Victorian State Government (VCA). Australian Cancer Research Foundation https://www.acrf.com.au/. National Breast Cancer Foundation https://nbcf.org.au/ (grant number ECF-15-002). Career Development Fellowship held by EMM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.