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| Status |
Public on Mar 19, 2024 |
| Title |
Chromatin remodeller Chd7 is developmentally regulated in the neural crest by tissue - specific transcription factors |
| Organism |
Gallus gallus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Neurocristopathies such as CHARGE syndrome result from aberrant neural crest development. A large proportion of CHARGE cases are attributed topathogenic variantsin the gene encoding CHD7, chromodomain helicase DNA binding protein 7, which remodels chromatin. While the role for CHD743in neural crest development is well documented,how this factor is specifically upregulated in neural crest cells is not understood. Here, we use epigenomic profiling of chick and human neural crest to identify a cohort of enhancers regulating Chd7 expression in neural crest cells and other tissues. We functionally validate upstream transcription factor binding at candidate enhancers, revealing novel epistatic relationships between neural crest master regulators and Chd7, showing tissue-specific regulation of a globally-acting chromatin remodeller for the first time. Furthermore, we find conserved enhancer features in human embryonic epigenomic data and validate the activity of the human equivalent CHD7 enhancers in the chick embryo. Our findings embed Chd7 in the neural crest gene regulatory network and offer potentially clinically relevant elements for interpreting CHARGE syndrome cases without causative allocation.
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| Overall design |
Transcription-factor binding determined by biotin ChIP-seq and Cut and Run for SOX10 and PAX7, respectively, in chick embryos.
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| Contributor(s) |
Williams RM, Candido-Ferreira I, Fountain D, Sauka-Spengler T |
| Citation missing |
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| |
| Submission date |
Mar 13, 2024 |
| Last update date |
Mar 20, 2024 |
| Contact name |
Tatjana Sauka-Spengler |
| E-mail(s) |
tatjana.sauka-spengler@imm.ox.ac.uk
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| Organization name |
MRC Weatherall Institute of Molecular Medicine
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| Department |
University of Oxford
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| Lab |
Sauka-Spengler lab
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| Street address |
Radcliffe Department of Medicine
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| City |
Oxford |
| State/province |
Oxfordshire |
| ZIP/Postal code |
OX3 9DS |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL19005 |
Illumina HiSeq 2500 (Gallus gallus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA1087293 |
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