Characterization of Chromatin Structure-associated Histone Modifications in Breast Cancer Cells

Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Korea.
Genomics & informatics 09/2012; 10(3):145-52. DOI: 10.5808/GI.2012.10.3.145
Source: PubMed


Chromatin structure and dynamics that are influenced by epigenetic marks, such as histone modification and DNA methylation, play a crucial role in modulating gene transcription. To understand the relationship between histone modifications and regulatory elements in breast cancer cells, we compared our chromatin immunoprecipitation sequencing (ChIP-Seq) histone modification patterns for histone H3K4me1, H3K4me3, H3K9/16ac, and H3K27me3 in MCF-7 cells with publicly available formaldehyde-assisted isolation of regulatory elements (FAIRE)-chip signals in human chromosomes 8, 11, and 12, identified by a method called FAIRE. Active regulatory elements defined by FAIRE were highly associated with active histone modifications, like H3K4me3 and H3K9/16ac, especially near transcription start sites. The H3K9/16ac-enriched genes that overlapped with FAIRE signals (FAIRE-H3K9/14ac) were moderately correlated with gene expression levels. We also identified functional sequence motifs at H3K4me1-enriched FAIRE sites upstream of putative promoters, suggesting that regulatory elements could be associated with H3K4me1 to be regarded as distal regulatory elements. Our results might provide an insight into epigenetic regulatory mechanisms explaining the association of histone modifications with open chromatin structure in breast cancer cells.

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Available from: Tae-Young Roh, May 28, 2014
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    • "found that regulatory active elements identified by formaldehyde-assisted isolation of regulatory elements (FAIRE) method were highly correlated with histone modifications, for instance H3K4me3 and H3K9/16ac, by comparing the pattern of histone modifications with regulatory elements (Hong et al., 2012). Heyn et al. analyzed high resolution DNA methylation profiles in 15 pairs of twins with inconsistent breast cancer, and then identified 403 differential methylation CG sites in known and new potential breast cancer genes(Heyn et al., 2013). "

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    • "of the ETS family, NRF1, GFY and GFX were also enriched. The less known GFY, ETS and NRF1 motifs were detected at start sites of MCF7 cells (Hong et al. 2012), while the core promoter specific ETS motif was detected earlier (Xie et al. 2005; Heinz et al. 2010), suggesting that these are general binding sites of the core promoter region. In contrast with the motif enrichments of H4ac, a bZIP motif with strong CG spacer (similar to CRE) and a clear IRF motif without the GGAA (ETS-specific) sequence were found. "
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