Functional elements demarcated by histone modifications in breast cancer cells

被引：17

作者：

Choe, Moon Kyung ^{[1
]}

Hong, Chang-Pyo ^{[1
]}

Park, Jihwan ^{[1
]}

Seo, Seong Hye ^{[1
]}

Roh, Tae-Young ^{[1
,2
]}

机构：

[1] POSTECH Pohang Univ Sci & Technol, Div Mol & Life Sci, Pohang 790784, Kyungbuk, South Korea

[2] POSTECH Pohang Univ Sci & Technol, Div Integrat Biosci & Biotechnol, Pohang 790784, Kyungbuk, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2012年 / 418卷 / 03期

基金：

新加坡国家研究基金会;

关键词：

Breast cancer; Histone modification; Epigenome; Regulatory elements; Enhancer; DNA METHYLATION; MODIFYING ENZYMES; GENOME; ACETYLATION; TRANSCRIPTION; ENHANCERS; PATTERNS; MARKERS;

D O I：

10.1016/j.bbrc.2012.01.042

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Histone modifications are regarded as one of markers to identify regulatory elements which are DNA segments modulating gene transcription. Aberrant changes of histone modification levels are frequently observed in cancer. We have employed ChIP-Seq to identify regulatory elements in human breast cancer cell line, MCF-7 by comparing histone modification patterns of H3K4me1, H3K4me3, and H3K9/14ac to those in normal mammary epithelial cell line, MCF-10A. The genome-wide analysis shows that H3K4me3 and H3K9/14ac are highly enriched at promoter regions and H3K4me1 has a relatively broad distribution over proximity of TSSs as well as other genomic regions. We identified that many differentially expressed genes in MCF-7 have divergent histone modification patterns. To understand the functional roles of distinctively histone-modified regions, we selected 35 genomic regions marked by at least one histone modification and located from 3 to 10 kb upstream of TSS in both MCF-7 and MCF-10A and assessed their transcriptional activities. About 66% and 60% of selected regions in MCF-7 and MCF-10A, respectively, enhanced the transcriptional activity. Interestingly, most regions marked by H3K4me1 exhibited an enhancer activity. Regions with two or more kinds of histone modifications did show varying activities. In conclusion, our data reflects that comprehensive analysis of histone modification profiles under cell type-specific chromatin environment should provide a better chance for defining functional regulatory elements in the genome. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：475 / 482

页数：8

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