Dynamic changes in the epigenomic landscape regulate human organogenesis and link to developmental disorders

Dave T. Gerrard, Andrew Berry, Rachel Jennings, Matthew Birket, Peyman Zarrineh, Myles Garstang, Sarah Withey, Patrick Short, Sandra Jiménez-Ganced, Panos N. Firbas, Ian Donaldson, Andy Sharrocks, Karen Piper Hanley, Matthew E. Hurles, Jose Luis Gomez-Skarmeta, Nicoletta Bobola, Neil Hanley

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number3920
Pages (from-to)3920
JournalNature Communications
Issue number1
Publication statusPublished - 6 Aug 2020


  • 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
  • Promoter Regions, Genetic
  • Tissue Distribution
  • Transcription Factors/metabolism
  • Zebrafish/embryology


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