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

Lowdon RF, Zhang B, Bilenky M, Mauro T, Li D, Gascard P, Sigaroudinia M, Farnham PJ, Bastian BC, Tlsty TD, Marra MA, Hirst M, Costello JF, Wang T, Cheng JB - Nat Commun (2014)

Bottom Line: This suggests that SE origin contributes to DNA methylation patterning, while shared skin tissue environment has limited effect on epidermal keratinocytes.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University in St Louis, St Louis, Missouri 63108, USA.

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.

Show MeSH

Related in: MedlinePlus

Developmental origins of samplesDevelopmental origins of skin and breast cell types utilized in this study. Embryonic surface ectoderm from the vertebrate neurula stage embryo (blue) gives rise to keratinocytes in the skin and cells of the mammary gland lumen. Embryonic neural crest cells (green) will produce melanocytes that intercalate with epidermal keratinocytes, and skin fibroblasts are derived from embryonic mesoderm (red).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4385735&req=5

Figure 1: Developmental origins of samplesDevelopmental origins of skin and breast cell types utilized in this study. Embryonic surface ectoderm from the vertebrate neurula stage embryo (blue) gives rise to keratinocytes in the skin and cells of the mammary gland lumen. Embryonic neural crest cells (green) will produce melanocytes that intercalate with epidermal keratinocytes, and skin fibroblasts are derived from embryonic mesoderm (red).

Mentions: To investigate how developmental origin and tissue environment contribute to cell type-specific epigenetic patterns, we utilize skin as a model system. The three most prevalent skin cell types are each derived from a different embryonic origin (keratinocytes from surface ectoderm, fibroblasts from mesoderm, and melanocytes from neural crest11), but exist within a shared tissue environment (Figure 1). We generate DNA methylation and histone modification profiles for these three skin cell types and compared their epigenomes among the skin cell types and against breast, blood, and brain tissue epigenomes. The three skin cell types share few regions with common DNA methylation and histone modification states, that were not also present in the other tissue samples. Surface-ectoderm derived skin keratinocytes and breast cells however, share many common differentially DNA methylated regions (SE-DMRs). SE-DMRs are enriched for enhancer- and promoter-associated histone modifications in SE-derived cell types and for binding motifs of relevant transcription factors. Reconstruction of the gene regulatory network connecting these transcription factors and putative target genes with nearby SE-DMRs demarcated epigenetic and regulatory events associated with structural components and signaling pathways in SE-derived cell types. Thus, for surface ectoderm-derived cells, their shared developmental origin influences their epigenomes to a greater extent than tissue environment. Furthermore, a shared gene regulatory network emerged from the SE-DMR signature.


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

Lowdon RF, Zhang B, Bilenky M, Mauro T, Li D, Gascard P, Sigaroudinia M, Farnham PJ, Bastian BC, Tlsty TD, Marra MA, Hirst M, Costello JF, Wang T, Cheng JB - Nat Commun (2014)

Developmental origins of samplesDevelopmental origins of skin and breast cell types utilized in this study. Embryonic surface ectoderm from the vertebrate neurula stage embryo (blue) gives rise to keratinocytes in the skin and cells of the mammary gland lumen. Embryonic neural crest cells (green) will produce melanocytes that intercalate with epidermal keratinocytes, and skin fibroblasts are derived from embryonic mesoderm (red).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4385735&req=5

Figure 1: Developmental origins of samplesDevelopmental origins of skin and breast cell types utilized in this study. Embryonic surface ectoderm from the vertebrate neurula stage embryo (blue) gives rise to keratinocytes in the skin and cells of the mammary gland lumen. Embryonic neural crest cells (green) will produce melanocytes that intercalate with epidermal keratinocytes, and skin fibroblasts are derived from embryonic mesoderm (red).
Mentions: To investigate how developmental origin and tissue environment contribute to cell type-specific epigenetic patterns, we utilize skin as a model system. The three most prevalent skin cell types are each derived from a different embryonic origin (keratinocytes from surface ectoderm, fibroblasts from mesoderm, and melanocytes from neural crest11), but exist within a shared tissue environment (Figure 1). We generate DNA methylation and histone modification profiles for these three skin cell types and compared their epigenomes among the skin cell types and against breast, blood, and brain tissue epigenomes. The three skin cell types share few regions with common DNA methylation and histone modification states, that were not also present in the other tissue samples. Surface-ectoderm derived skin keratinocytes and breast cells however, share many common differentially DNA methylated regions (SE-DMRs). SE-DMRs are enriched for enhancer- and promoter-associated histone modifications in SE-derived cell types and for binding motifs of relevant transcription factors. Reconstruction of the gene regulatory network connecting these transcription factors and putative target genes with nearby SE-DMRs demarcated epigenetic and regulatory events associated with structural components and signaling pathways in SE-derived cell types. Thus, for surface ectoderm-derived cells, their shared developmental origin influences their epigenomes to a greater extent than tissue environment. Furthermore, a shared gene regulatory network emerged from the SE-DMR signature.

Bottom Line: This suggests that SE origin contributes to DNA methylation patterning, while shared skin tissue environment has limited effect on epidermal keratinocytes.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University in St Louis, St Louis, Missouri 63108, USA.

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.

Show MeSH
Related in: MedlinePlus