Functional elements demarcated by histone modifications in breast cancer cells

Moon Kyung Choe; Chang Pyo Hong; Jihwan Park; Seong Hye Seo; Tae Young Roh

doi:10.1016/j.bbrc.2012.01.042

Functional elements demarcated by histone modifications in breast cancer cells

Moon Kyung Choe, Chang Pyo Hong, Jihwan Park, Seong Hye Seo, Tae Young Roh

Department of Life Science

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	475-482
Number of pages	8
Journal	Biochemical and Biophysical Research Communications
Volume	418
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2012.01.042
State	Published - 17 Feb 2012

Bibliographical note

Funding Information:
We thank members of Lab. of System Genomics, POSTECH, for active discussion and Dr. Y.K. Shin, Seoul National University for kindly providing MCF-7. This work was supported by National Research Foundation (KRF-2008-313- C00665 , 2010-0023412, and 2010-0026759), Korea Healthcare technology R&D Project , MHWFA (A084519), and the World Class University program , NRF, MEST (R31-10105), Republic of Korea.

Keywords

Breast cancer
Enhancer
Epigenome
Histone modification
Regulatory elements

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbrc.2012.01.042

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title = "Functional elements demarcated by histone modifications in breast cancer cells",

abstract = "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.",

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author = "Choe, {Moon Kyung} and Hong, {Chang Pyo} and Jihwan Park and Seo, {Seong Hye} and Roh, {Tae Young}",

note = "Funding Information: We thank members of Lab. of System Genomics, POSTECH, for active discussion and Dr. Y.K. Shin, Seoul National University for kindly providing MCF-7. This work was supported by National Research Foundation (KRF-2008-313- C00665 , 2010-0023412, and 2010-0026759), Korea Healthcare technology R&D Project , MHWFA (A084519), and the World Class University program , NRF, MEST (R31-10105), Republic of Korea. ",

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AU - Roh, Tae Young

N1 - Funding Information: We thank members of Lab. of System Genomics, POSTECH, for active discussion and Dr. Y.K. Shin, Seoul National University for kindly providing MCF-7. This work was supported by National Research Foundation (KRF-2008-313- C00665 , 2010-0023412, and 2010-0026759), Korea Healthcare technology R&D Project , MHWFA (A084519), and the World Class University program , NRF, MEST (R31-10105), Republic of Korea.

PY - 2012/2/17

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N2 - 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.

AB - 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.

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KW - Enhancer

KW - Epigenome

KW - Histone modification

KW - Regulatory elements

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SN - 0006-291X

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JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 3

ER -

Functional elements demarcated by histone modifications in breast cancer cells

Abstract

Bibliographical note

Keywords

UN SDGs

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