PUBLICATION
Dynamic changes in the epigenomic landscape regulate human organogenesis and link to developmental disorders
- Authors
- Gerrard, D.T., Berry, A.A., Jennings, R.E., Birket, M.J., Zarrineh, P., Garstang, M.G., Withey, S.L., Short, P., Jiménez-Gancedo, S., Firbas, P.N., Donaldson, I., Sharrocks, A.D., Hanley, K.P., Hurles, M.E., Gomez-Skarmeta, J.L., Bobola, N., Hanley, N.A.
- ID
- ZDB-PUB-200810-19
- Date
- 2020
- Source
- Nature communications 11: 3920 (Journal)
- Registered Authors
- Sharrocks, Andrew D.
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Databases, Genetic
- Developmental Disabilities/genetics*
- Enhancer Elements, Genetic
- Epigenesis, Genetic*
- Gene Expression Regulation, Developmental
- Histone Code/genetics
- Humans
- Models, Genetic
- Mutation
- Organogenesis/genetics*
- Organogenesis/physiology
- Promoter Regions, Genetic
- Tissue Distribution
- Transcription Factors/metabolism
- Zebrafish/embryology
- Zebrafish/genetics
- PubMed
- 32764605 Full text @ Nat. Commun.
Citation
Gerrard, D.T., Berry, A.A., Jennings, R.E., Birket, M.J., Zarrineh, P., Garstang, M.G., Withey, S.L., Short, P., Jiménez-Gancedo, S., Firbas, P.N., Donaldson, I., Sharrocks, A.D., Hanley, K.P., Hurles, M.E., Gomez-Skarmeta, J.L., Bobola, N., Hanley, N.A. (2020) Dynamic changes in the epigenomic landscape regulate human organogenesis and link to developmental disorders. Nature communications. 11:3920.
Abstract
How the genome activates or silences transcriptional programmes governs organ formation. Little is known in human embryos undermining our ability to benchmark the fidelity of stem cell differentiation or cell programming, or interpret the pathogenicity of noncoding variation. Here, we study histone modifications across thirteen tissues during human organogenesis. We integrate the data with transcription to build an overview of how the human genome differentially regulates alternative organ fates including by repression. Promoters from nearly 20,000 genes partition into discrete states. Key developmental gene sets are actively repressed outside of the appropriate organ without obvious bivalency. Candidate enhancers, functional in zebrafish, allow imputation of tissue-specific and shared patterns of transcription factor binding. Overlaying more than 700 noncoding mutations from patients with developmental disorders allows correlation to unanticipated target genes. Taken together, the data provide a comprehensive genomic framework for investigating normal and abnormal human development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping