Histone H3 lysine 4 acetylation and methylation dynamics define breast cancer subtypes

Oncotarget
Terri L MessierGary S Stein

Abstract

The onset and progression of breast cancer are linked to genetic and epigenetic changes that alter the normal programming of cells. Epigenetic modifications of DNA and histones contribute to chromatin structure that result in the activation or repression of gene expression. Several epigenetic pathways have been shown to be highly deregulated in cancer cells. Targeting specific histone modifications represents a viable strategy to prevent oncogenic transformation, tumor growth or metastasis. Methylation of histone H3 lysine 4 has been extensively studied and shown to mark genes for expression; however this residue can also be acetylated and the specific function of this alteration is less well known. To define the relative roles of histone H3 methylation (H3K4me3) and acetylation (H3K4ac) in breast cancer, we determined genomic regions enriched for both marks in normal-like (MCF10A), transformed (MCF7) and metastatic (MDA-MB-231) cells using a genome-wide ChIP-Seq approach. Our data revealed a genome-wide gain of H3K4ac associated with both early and late breast cancer cell phenotypes, while gain of H3K4me3 was predominantly associated with late stage cancer cells. Enrichment of H3K4ac was over-represented at promoters of genes ...Continue Reading

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Citations

May 11, 2017·Journal of Cellular Physiology·Kirsten M TracyGary S Stein
Mar 2, 2019·PLoS Computational Biology·Jingyu ZhangJianhua Xing
Apr 12, 2019·International Journal of Molecular Sciences·Peter KubatkaDietrich Büsselberg
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Dec 7, 2017·Oncotarget·Chengcheng ZhangQi Li
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Apr 17, 2021·EMBO Reports·Isabel Castro-PiedrasKevin Pruitt

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Datasets Mentioned

BETA
GSE75169

Methods Mentioned

BETA
acetylation
ChIP-seq
RNA-seq
ESR
immunoprecipitation
ChIP
PCR

Software Mentioned

FastX
NGSplot
CHARAFE
fastq Tophat
GOZGIT
Ilumina
UCSC genome browser
Fastqc
cutadapt
IDR

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