Characterization of Chromatin Structure-associated Histone Modifications in Breast Cancer Cells
ABSTRACT 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.
SourceAvailable from: Jihwan Park[Show abstract] [Hide abstract]
ABSTRACT: The transcriptional silencing of human immunodeficiency virus type 1 (HIV-1) provirus in latently infected cells is a major hurdle on the pathway to HIV-1 elimination. The epigenetic mechanisms established by histone modifications may affect the transcriptional silencing of HIV-1 and viral latency. A systematic epigenome profiling could be applicable to develop new epigenetic diagnostic markers for detecting HIV-1 latency. The HIV-1 latency cell lines (NCHA1, NCHA2, and ACH2) were compared to CD4 T cell line (A3.01). The histone modification profiles obtained from chromatin immunoprecipiation followed by sequencing (ChIP-Seq) for histone H3K4me3 and H3K9ac were systematically examined and differential gene expression patterns along with levels of histone modifications were used for network analysis. The HIV-1 latency gave rise to down-regulation of histone H3K4me3 and H3K9ac levels in 387 and 493 regions and up-regulation in 451 and 962 sites, respectively. By network analysis, 5 gene clusters were associated with down-regulated histone modifications and 6 gene clusters came up with up-regulated histone modifications. Integration of gene expression with epigenetic information revealed that the cell cycle regulatory genes such as CDKN1A (p21) and cyclin D2 (CCND2) identified by differentially modified histones might be an important role in maintaining the HIV-1 latency. The transcriptional regulation by epigenetic memory should play a key role in the evolution and maintenance of HIV-1 latency accompanied by modulation of signaling molecules in the host cells.AIDS (London, England) 04/2014; 28(12). DOI:10.1097/QAD.0000000000000309 · 6.56 Impact Factor
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ABSTRACT: Stable introduction of a functional gene in hematopoietic progenitor cells (HPCs) has appeared to be an alternative approach to correct genetically linked blood diseases. However, it is still unclear whether lentiviral vector (LV) is subjected to gene silencing in HPCs. Here, we show that LV carrying green fluorescent protein (GFP) reporter gene driven by cytomegalovirus (CMV) promoter was subjected to transgene silencing after transduction into HPCs. This phenomenon was not due to the deletion of proviral copy number. Study using DNA demethylating agent and histone deacetylase (HDAC) inhibitor showed that the drugs could either prevent or reverse the silencing effect. Using sodium bisulfite sequencing and chromatin immunoprecipitation (ChIP) assay, we demonstrated that DNA methylation occurred soon after LV transduction. At the highest level of gene expression, CMV promoter was acetylated and was in a euchromatin state, while GFP reporter gene was acetylated but was strangely in a heterochromatin state. When the expression declined, CMV promoter underwent transition from acetylated and euchromatic state to a heterochromatic state, while the GFP reporter gene was in deacetylated and heterochromatic state. With these, we verify that DNA methylation and dynamic histone modifications lead to transgene silencing in HPCs transduced with LV.01/2015; 2015:1-11. DOI:10.1155/2015/346134
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ABSTRACT: Polycomb group (PcG) proteins play an important role in the regulation of gene expression, especially genes encoding lineage-specific factors. Perturbations in PcG protein expression may trigger an unexpected developmental pathway, resulting in birth defects and developmental disabilities. Two Polycomb repressive complexes, PRC1 and PRC2, have been identified and are related with diverse cellular processes through histone modifications. Many developmental genes are trimethylated at histone H3 lysine 27 (H3K27me3) mediated by PRC2, which provides a binding site for PRC1. These processes contribute to chromatin compaction and transcriptional repression. In this review, we discuss about the complex formation of PcG proteins, the mechanism through which they are recruited to target sites and their functional roles in cell differentiation.Epigenomics 02/2015; 7(1):75-84. DOI:10.2217/epi.14.61 · 5.22 Impact Factor