Epigenetic and transcriptional determinants of the human breast.
Epigenetic and transcriptional determinants of the human breast.
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DOI：
10.1038/ncomms7351
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发表时间：
2015-02-18
影响因子：
16.6
通讯作者：
Hirst, Martin
中科院分区：
文献类型：
--
作者：
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
尽管大量的研究都致力于描述与产前分化相关的表观遗传变化，但对伴随出生后分化而来的表观遗传变化却知之甚少，而出生后分化是寿命有限的功能完全分化细胞类型出现的地方。在这里，我们试图通过从无疾病的人类受试者中分离的原代人乳腺细胞类型生成表观基因组和转录谱来解决这一差距。根据这些数据，我们定义了一个全面的人类乳腺转录网络，包括一组肌上皮和管腔上皮特异性内含子保留事件。表观遗传状态与来自不同乳腺上皮谱系的RNA表达的交叉表明，mCpG提供了稳定的外显子和内含子使用记录，而H3K36me3是动态的。我们发现在管腔细胞和肌上皮细胞类型之间的表观基因组重编程存在显著的不对称性，与肌上皮细胞相比，管腔细胞的基因组中含有两倍多的低甲基化增强子元件。与产后分化相关的表观遗传变化已被表征。在这里，作者从原代人乳腺细胞中生成了表观基因组和转录谱，为体内定义出生后细胞分化的转录和表观遗传事件提供了见解。
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.
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影响因子：
3.7
作者：
Butterfield YS;Kreitzman M;Thiessen N;Corbett RD;Li Y;Pang J;Ma YP;Jones SJ;Birol İ
通讯作者：
Birol İ
影响因子：
44.1
作者：
通讯作者：
--
影响因子：
64.5
作者：
Gifford CA;Ziller MJ;Gu H;Trapnell C;Donaghey J;Tsankov A;Shalek AK;Kelley DR;Shishkin AA;Issner R;Zhang X;Coyne M;Fostel JL;Holmes L;Meldrim J;Guttman M;Epstein C;Park H;Kohlbacher O;Rinn J;Gnirke A;Lander ES;Bernstein BE;Meissner A
通讯作者：
Meissner A
影响因子：
2.9
作者：
OHARE, MJ;ORMEROD, MG;GUSTERSON, BA
通讯作者：
GUSTERSON, BA
影响因子：
8
作者：
Meyer, KM;Hess, SM;Leadon, SA
通讯作者：
Leadon, SA