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Chromatin remodeller Chd7 is developmentally regulated in the neural crest by tissue-specific transcription factors
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Chromatin remodeller Chd7 is developmentally regulated in the neural crest by tissue-specific transcription factors
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Journal Article
Chromatin remodeller Chd7 is developmentally regulated in the neural crest by tissue-specific transcription factors
2024
Overview
Neurocristopathies such as CHARGE syndrome result from aberrant neural crest development. A large proportion of CHARGE cases are attributed to pathogenic variants in the gene encoding CHD7, chromodomain helicase DNA binding protein 7, which remodels chromatin. While the role for CHD7 in neural crest development is well documented, how this factor is specifically up-regulated 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. 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.
Publisher
Public Library of Science
Subject
/ Animals
/ CHARGE Syndrome - metabolism
/ Chromatin Assembly and Disassembly - genetics
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - metabolism
/ Embryos
/ Enhancer Elements, Genetic - genetics
/ Gene Expression Regulation, Developmental
/ Genes
/ Humans
/ Medicine and Health Sciences
/ Mutation
/ Organ Specificity - genetics
/ Research and Analysis Methods
