Regulatory network decoded from epigenomes of surface ectoderm-derived cell types

Rebecca F. Lowdon, Bo Zhang, Misha Bilenky, Thea Mauro, Daofeng Li, Philippe Gascard, Mahvash Sigaroudinia, Peggy J. Farnham, Boris C. Bastian, Thea D. Tlsty, Marco A. Marra, Martin Hirst, Joseph F. Costello, Ting Wang and Jeffrey B. Cheng ()
Additional contact information
Rebecca F. Lowdon: Center for Genome Sciences and Systems Biology, Washington University in St Louis
Bo Zhang: Center for Genome Sciences and Systems Biology, Washington University in St Louis
Misha Bilenky: Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency
Thea Mauro: University of California, San Francisco
Daofeng Li: Center for Genome Sciences and Systems Biology, Washington University in St Louis
Philippe Gascard: Center for Translational Research in the Molecular Genetics of Cancer, University of California, San Francisco
Mahvash Sigaroudinia: Center for Translational Research in the Molecular Genetics of Cancer, University of California, San Francisco
Peggy J. Farnham: Norris Comprehensive Cancer Center, University of Southern California
Boris C. Bastian: University of California, San Francisco
Thea D. Tlsty: Center for Translational Research in the Molecular Genetics of Cancer, University of California, San Francisco
Marco A. Marra: Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency
Martin Hirst: Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency
Joseph F. Costello: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco
Ting Wang: Center for Genome Sciences and Systems Biology, Washington University in St Louis
Jeffrey B. Cheng: University of California, San Francisco

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: Abstract Developmental history shapes the epigenome and biological function of differentiated cells. Epigenomic patterns have been broadly attributed to the three embryonic germ layers. Here we investigate how developmental origin influences epigenomes. We compare key epigenomes of cell types derived from surface ectoderm (SE), including keratinocytes and breast luminal and myoepithelial cells, against neural crest-derived melanocytes and mesoderm-derived dermal fibroblasts, to identify SE differentially methylated regions (SE-DMRs). DNA methylomes of neonatal keratinocytes share many more DMRs with adult breast luminal and myoepithelial cells than with melanocytes and fibroblasts from the same neonatal skin. This suggests that SE origin contributes to DNA methylation patterning, while shared skin tissue environment has limited effect on epidermal keratinocytes. Hypomethylated SE-DMRs are in proximity to genes with SE relevant functions. They are also enriched for enhancer- and promoter-associated histone modifications in SE-derived cells, and for binding motifs of transcription factors important in keratinocyte and mammary gland biology. Thus, epigenomic analysis of cell types with common developmental origin reveals an epigenetic signature that underlies a shared gene regulatory network.

Date: 2014
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DOI: 10.1038/ncomms6442

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