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Epigenetic and transcriptional determinants of the human breast

2015; Nature Portfolio; Volume: 6; Issue: 1 Linguagem: Inglês

10.1038/ncomms7351

2041-1723

Philippe Gascard, Misha Bilenky, Mahvash Sigaroudinia, Jianxin Zhao, Luolan Li, Annaïck Carles, Allen Delaney, Angela Tam, Baljit Kamoh, Stephanie Cho, Malachi Griffith, Andy Chu, Gordon Robertson, Dorothy Cheung, Irene Li, Alireza Heravi‐Moussavi, Michelle Moksa, Matthew Mingay, Angela Hussainkhel, Brad Davis, Raman P. Nagarajan, Chibo Hong, Lorigail Echipare, Henriette O’Geen, Matthew J. Hangauer, Jeffrey B. Cheng, Dana S. Neel, Donglei Hu, Michael T. McManus, Richard A. Moore, Andrew J. Mungall, Yussanne Ma, Patrick Plettner, Elad Ziv, Ting Wang, Peggy Farnham, Steven J.M. Jones, Marco A. Marra, Thea D. Tlsty, J Costello, Martin Hirst,

RNA modifications and cancer

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.