Nucleosome positioning and histone modifications define relationships between regulatory elements and nearby gene expression in breast epithelial cells

BMC Genomics

Gerhard A Coetzee²  Houtan Noushmehr³  Chunli Yan¹  Simon G Coetzee³  Dennis J Hazelett¹  Suhn Kyong Rhie¹ 

[1]Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA

[2]Urology, Microbiology and Preventive Medicine, USC/Norris Cancer Center, NOR 6411, Keck School of Medicine, 1441 Eastlake Ave, Los Angeles, CA 90089-9176, USA

[3]Present Address: Department of Genetics, Faculty of Medicine in Ribeirão Preto, University of São Paulo, 14049-900 São Paulo, Brazil

关键词: Genes;    Transcription factors;    Promoters;    Enhancers;    Nucleosomes;    Epigenetics;    Breast epithelial cells;   

Others  :  1217299
DOI  :  10.1186/1471-2164-15-331

 received in 2013-11-28, accepted in 2014-04-24,  发布年份 2014

【 摘 要 】

Background

The 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).

Results

Enhancers 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.

Conclusions

These 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.

【 授权许可】

   
2014 Rhie et al.; licensee BioMed Central Ltd.

【 图 表 】

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