Epigenetic and transcriptional determinants of the human breast

• Published in: Nature communications Vol. 6; no. 1; p. 6351
• Main Authors: Gascard, Philippe, Bilenky, Misha, Sigaroudinia, Mahvash, Zhao, Jianxin, Li, Luolan, Carles, Annaick, Delaney, Allen, Tam, Angela, Kamoh, Baljit, Cho, Stephanie, Griffith, Malachi, Chu, Andy, Robertson, Gordon, Cheung, Dorothy, Li, Irene, Heravi-Moussavi, Alireza, Moksa, Michelle, Mingay, Matthew, Hussainkhel, Angela, Davis, Brad, Nagarajan, Raman P., Hong, Chibo, Echipare, Lorigail, O’Geen, Henriette, Hangauer, Matthew J., Cheng, Jeffrey B., Neel, Dana, Hu, Donglei, McManus, Michael T., Moore, Richard, Mungall, Andrew, Ma, Yussanne, Plettner, Patrick, Ziv, Elad, Wang, Ting, Farnham, Peggy J., Jones, Steven J.M., Marra, Marco A., Tlsty, Thea D., Costello, Joseph F., Hirst, Martin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.02.2015; Nature Publishing Group; Nature Pub. Group
• Subjects: 13/51; 38/15; 38/23; 38/77; 38/91; 631/136/532/2436; 631/337/572; 631/61/212/177; 631/67/1347; Breast - cytology; Breast - metabolism; Cell Cycle; Cell Differentiation; Cell Separation; Chromatin - chemistry; Chromatin Immunoprecipitation; CpG Islands; Epigenesis, Genetic; Epigenomics; Epithelial Cells - cytology; Exons; Female; Flow Cytometry; Gene Expression Regulation; Genome, Human; Histones - chemistry; Humanities and Social Sciences; Humans; Introns; Karyotyping; MicroRNAs - metabolism; multidisciplinary; Science; Science (multidisciplinary); Sequence Analysis, RNA; Transcription, Genetic
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms7351

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. Epigenetic changes associated with post-natal differentiation have been characterized. Here the authors generate epigenomic and transcriptional profiles from primary human breast cells, providing insights into the transcriptional and epigenetic events that define post-natal cell differentiation in vivo .