Dynamic changes in the epigenomic landscape regulate human organogenesis and link to developmental disorders
AuthorsGerrard, Dave T.; orcid: 0000-0001-6890-7213
Berry, Andrew A.
Jennings, Rachel E.
Birket, Matthew J.; orcid: 0000-0002-5985-6626
Garstang, Myles G.
Withey, Sarah L.
Short, Patrick; orcid: 0000-0002-7626-6177
Firbas, Panos N.
Donaldson, Ian; orcid: 0000-0002-0032-0931
Sharrocks, Andrew D.
Hanley, Karen Piper; orcid: 0000-0001-9473-9647
Hurles, Matthew E.
Gomez-Skarmeta, José Luis
Hanley, Neil A.; orcid: 0000-0003-3234-4038; email: email@example.com
MetadataShow full item record
AbstractAbstract: 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.
CitationNature Communications, volume 11, issue 1, page 3920
PublisherNature Publishing Group UK
DescriptionFrom Springer Nature via Jisc Publications Router
History: received 2019-10-04, accepted 2020-06-18, registration 2020-06-24, pub-electronic 2020-08-06, online 2020-08-06, collection 2020-12
Publication status: Published
Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265; Grant(s): CRTF, PhD studentship, MR/J003352/1, MR/L009986/1, MR/L009986/1, MR/S036121/1, MR/000638/1
Funder: Academy of Medical Sciences; doi: https://doi.org/10.13039/501100000691; Grant(s): Lecturer starter grant
Funder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440; Grant(s): 088566, 097820, 105610
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