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BMC Genomics

, 15:331

Human and rodent genomics

Abstract

BackgroundThe precise nature of how cell type specific chromatin structures at enhancer sites affect gene expression is largely unknown. Here we identified cell type specific enhancers coupled with gene expression in two different types of breast epithelial cells, HMEC normal breast epithelial cells and MDAMB231 triple negative breast cancer cell line.

ResultsEnhancers were defined by modified neighboring histones using chromatin immunoprecipitation followed by sequencing ChIP-seq and nucleosome depletion using formaldehyde-assisted isolation of regulatory elements followed by sequencing FAIRE-seq. Histone modifications at enhancers were related to the expression levels of nearby genes up to 750 kb away. These expression levels were correlated with enhancer status poised or active, defined by surrounding histone marks. Furthermore, about fifty percent of poised and active enhancers contained nucleosome-depleted regions. We also identified response element motifs enriched at these enhancer sites that revealed key transcription factors e.g. TP63 likely involved in regulating breast epithelial enhancer-mediated gene expression. By utilizing expression data, potential target genes of more than 600 active enhancers were identified. These genes were involved in proteolysis, epidermis development, cell adhesion, mitosis, cell cycle, and DNA replication.

ConclusionsThese findings facilitate the understanding of epigenetic regulation specifically, such as the relationships between regulatory elements and gene expression and generally, how breast epithelial cellular phenotypes are determined by cell type specific enhancers.

KeywordsBreast epithelial cells Epigenetics Nucleosomes Enhancers Promoters Transcription factors Genes AbbreviationsBCaBreast cancer

H3K4Lysine 4 of histone 3

me1Monomethyl

me2Dimethyl

me3Trimethyl

H3K9acAcetylated lysine 9 of histone 3

H3K14acAcetylated lysine 14 of histone 3

H3K27acAcetylated lysine 27 of histone 3

ChIPChromatin immunoprecipitation

FAIREFormaldehyde Assisted Isolation of Regulatory Elements

TSSTranscription Start Site

TTSTranscription Termination Site

HSELHMEC specific enhancer loci

MSELMDAMB231 specific enhancer loci.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2164-15-331 contains supplementary material, which is available to authorized users.

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Autor: Suhn Kyong Rhie - Dennis J Hazelett - Simon G Coetzee - Chunli Yan - Houtan Noushmehr - Gerhard A Coetzee

Fuente: https://link.springer.com/



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