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Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
Regulatory network decoded from epigenomes of surface ectoderm-derived cell types.
Rebecca F Lowdon1, Bo Zhang1, Misha Bilenky2
1Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University in St Louis, St Louis, Missouri 63108, USA.
Developmental origin shapes cell epigenomes. Surface ectoderm (SE)-derived cells share unique DNA methylation patterns, revealing an epigenetic signature linked to shared gene regulatory networks.
Area of Science:
- Developmental biology
- Epigenetics
- Cell biology
Background:
- Cellular function and epigenomic patterns are influenced by developmental origins.
- Epigenomic patterns are often linked to the three embryonic germ layers.
- Understanding how developmental origin impacts epigenomes is crucial.
Purpose of the Study:
- To investigate the influence of developmental origin on cellular epigenomes.
- To identify surface ectoderm (SE)-differentially methylated regions (SE-DMRs).
- To compare epigenomes of SE-derived cells with those from other germ layers.
Main Methods:
- Comparative epigenomic analysis of cell types derived from surface ectoderm (SE), neural crest, and mesoderm.
- DNA methylome profiling of keratinocytes, breast luminal and myoepithelial cells, melanocytes, and dermal fibroblasts.
- Identification and characterization of SE-differentially methylated regions (SE-DMRs).
Main Results:
- Neonatal keratinocytes share more DNA methylation patterns with adult breast cells (SE-derived) than with melanocytes or fibroblasts.
- Surface ectoderm origin significantly contributes to DNA methylation patterning, independent of the immediate tissue environment.
- Hypomethylated SE-DMRs are located near genes with SE-relevant functions and are enriched for regulatory elements and transcription factor binding sites.
Conclusions:
- Epigenomic analysis of cells with common developmental origins reveals a distinct epigenetic signature.
- This signature reflects a shared gene regulatory network underlying cell function.
- Developmental origin is a key determinant of epigenomic patterning in differentiated cells.
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