title: Regulatory network decoded from epigenomes of surface ectoderm-derived cell types.
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.
authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University in St Louis, St Louis, Missouri 63108, USA.
authors.forename: Rebecca F
authors.initials: RF
authors.lastname: Lowdon
authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University in St Louis, St Louis, Missouri 63108, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3.
authors.forename: Misha
authors.initials: M
authors.lastname: Bilenky
authors.affiliation: Department of Dermatology, University of California, San Francisco, San Francisco, California 94143, USA.
authors.forename: Thea
authors.initials: T
authors.lastname: Mauro
authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University in St Louis, St Louis, Missouri 63108, USA.
authors.forename: Daofeng
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pathology, Center for Translational Research in the Molecular Genetics of Cancer, University of California, San Francisco, San Francisco, California 94143, USA.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gascard
authors.affiliation: Department of Pathology, Center for Translational Research in the Molecular Genetics of Cancer, University of California, San Francisco, San Francisco, California 94143, USA.
authors.forename: Mahvash
authors.initials: M
authors.lastname: Sigaroudinia
authors.affiliation: Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Peggy J
authors.initials: PJ
authors.lastname: Farnham
authors.affiliation: Department of Dermatology, University of California, San Francisco, San Francisco, California 94143, USA.
authors.forename: Boris C
authors.initials: BC
authors.lastname: Bastian
authors.affiliation: Department of Pathology, Center for Translational Research in the Molecular Genetics of Cancer, University of California, San Francisco, San Francisco, California 94143, USA.
authors.forename: Thea D
authors.initials: TD
authors.lastname: Tlsty
authors.affiliation: 1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3 [2] University of British Columbia, Department of Medical Genetics, Vancouver, British Columbia, Canada V6H 3N1.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Marra
authors.affiliation: 1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3 [2] Centre for High-Throughput Biology, Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
authors.forename: Martin
authors.initials: M
authors.lastname: Hirst
authors.affiliation: Department of Neurological Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California 94143, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Costello
authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University in St Louis, St Louis, Missouri 63108, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Dermatology, University of California, San Francisco, San Francisco, California 94143, USA.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Cheng
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D019175:DNA Methylation; D004475:Ectoderm / Q000166:cytology / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D053263:Gene Regulatory Networks; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013045:Species Specificity