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人类乳腺上皮细胞中细胞类型特异性表达模式的表观遗传调控。

Epigenetic regulation of cell type-specific expression patterns in the human mammary epithelium.

机构信息

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.

出版信息

PLoS Genet. 2011 Apr;7(4):e1001369. doi: 10.1371/journal.pgen.1001369. Epub 2011 Apr 21.

DOI:10.1371/journal.pgen.1001369
PMID:21533021
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3080862/
Abstract

Differentiation is an epigenetic program that involves the gradual loss of pluripotency and acquisition of cell type-specific features. Understanding these processes requires genome-wide analysis of epigenetic and gene expression profiles, which have been challenging in primary tissue samples due to limited numbers of cells available. Here we describe the application of high-throughput sequencing technology for profiling histone and DNA methylation, as well as gene expression patterns of normal human mammary progenitor-enriched and luminal lineage-committed cells. We observed significant differences in histone H3 lysine 27 tri-methylation (H3K27me3) enrichment and DNA methylation of genes expressed in a cell type-specific manner, suggesting their regulation by epigenetic mechanisms and a dynamic interplay between the two processes that together define developmental potential. The technologies we developed and the epigenetically regulated genes we identified will accelerate the characterization of primary cell epigenomes and the dissection of human mammary epithelial lineage-commitment and luminal differentiation.

摘要

分化是一个表观遗传程序，涉及多能性的逐渐丧失和获得细胞类型特异性特征。要理解这些过程，需要对表观遗传和基因表达谱进行全基因组分析，由于可用的细胞数量有限，这在原代组织样本中具有挑战性。在这里，我们描述了高通量测序技术在分析组蛋白和 DNA 甲基化以及正常人类乳腺祖细胞富集和腔系定向细胞的基因表达模式中的应用。我们观察到以细胞类型特异性方式表达的基因的组蛋白 H3 赖氨酸 27 三甲基化（H3K27me3）富集和 DNA 甲基化存在显著差异，表明它们受表观遗传机制调控，以及这两个过程之间的动态相互作用，共同决定了发育潜能。我们开发的技术和鉴定的受表观遗传调控的基因将加速对原代细胞表观基因组的特征描述以及对人类乳腺上皮谱系定向和腔系分化的剖析。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59aa/3080862/4ea8bf7e248e/pgen.1001369.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59aa/3080862/9a9c56885823/pgen.1001369.g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59aa/3080862/ecda61d69d8b/pgen.1001369.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59aa/3080862/3d978f23a26c/pgen.1001369.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59aa/3080862/61d0169f8c15/pgen.1001369.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59aa/3080862/940e80389536/pgen.1001369.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59aa/3080862/4ea8bf7e248e/pgen.1001369.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59aa/3080862/9a9c56885823/pgen.1001369.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59aa/3080862/c8ac912675b6/pgen.1001369.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59aa/3080862/ecda61d69d8b/pgen.1001369.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59aa/3080862/3d978f23a26c/pgen.1001369.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59aa/3080862/61d0169f8c15/pgen.1001369.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59aa/3080862/940e80389536/pgen.1001369.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59aa/3080862/4ea8bf7e248e/pgen.1001369.g007.jpg

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