Chromatin remodeller Chd7 is developmentally regulated in the neural crest by tissue - specific transcription factors
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ABSTRACT:
PROVIDER: PRJNA1087293 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28330447_1.fastq.gz | Fastqsanger.gz | |||
| SRR28330447_2.fastq.gz | Fastqsanger.gz | |||
| SRR28330448_1.fastq.gz | Fastqsanger.gz | |||
| SRR28330448_2.fastq.gz | Fastqsanger.gz | |||
| SRR28330449_1.fastq.gz | Fastqsanger.gz |
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Project description: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 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.
2024-09-16 | GSE270155 | GEO
Project description: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.
2024-03-19 | GSE261486 | GEO
Project description: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.
2024-09-16 | GSE262042 | GEO
Project description:Chromatin remodeller Chd7 is developmentally regulated in the neural crest by tissue-specific transcription factors
| PRJNA1125354 | ENA
Project description:Chromatin remodeller Chd7 is developmentally regulated in the neural crest by tissue - specific transcription factors (ATAC-Seq)
| PRJNA1090083 | ENA
Project description:Heterozygous loss-of function mutations in CHD7 (chromodomain helicase DNA-binding protein 7) lead to CHARGE syndrome, a complex developmental disorder affecting craniofacial structures, peripheral nerves and several organ systems like eyes, ears, nose and heart. Recently, it was demonstrated that CHD7 is essential for the formation of multipotent migratory neural crest cells, which migrate from the neural tube to many regions of the embryo, where they differentiate into various tissues including craniofacial and heart structures. So far only few CHD7 target genes involved in neural crest cell development have been identified and the role of CHD7 in neural crest cell guidance and the regulation of mesenchymal-epithelial transition is unknown. Therefore, we undertook a genome-wide microarray expression analysis on wild-type and CHD7 deficient (Chd7Whi/+ and Chd7Whi/Whi) mouse embryos at day 9.5, the time point of neural crest cell migration. We identified 98 genes showing greater than two fold differences in expression (log2 fold-change) and a P-value to false discovery rate (FDR) < 0.05 between wild-type and Chd7Whi/Whi embryos. Interestingly, many misregulated genes are involved in neural crest cell and axon guidance like semaphorins and ephrin receptors. By performing knockdown experiments for Chd7 and one of its target genes, namely semaphorin3a in Xenopus laevis embryos, we could show abnormalities in the migration of neural crest cells in vivo. Additionally, we detected non-synonymous SEMA3A variations in 3 out of 45 CHD7 negative CHARGE patients suggesting a role for SEMA3A in the pathogenesis of CHARGE syndrome. To identify genes that are affected by the absence of functional Chd7 at the time point of neural crest cell migration, the expression profiles of E9.5 wild-type, Chd7Whi/+ and Chd7Whi/Whi female mouse embryos were compared by whole-genome microarray analysis. Mouse embryos of the same sex were used to avoid sex-dependent gene expression effects. We performed microarray analysis by using the Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Agilent) on four biological replicates from each group.
2014-07-01 | E-GEOD-46591 | biostudies-arrayexpress
Project description:Heterozygous loss-of function mutations in CHD7 (chromodomain helicase DNA-binding protein 7) lead to CHARGE syndrome, a complex developmental disorder affecting craniofacial structures, peripheral nerves and several organ systems like eyes, ears, nose and heart. Recently, it was demonstrated that CHD7 is essential for the formation of multipotent migratory neural crest cells, which migrate from the neural tube to many regions of the embryo, where they differentiate into various tissues including craniofacial and heart structures. So far only few CHD7 target genes involved in neural crest cell development have been identified and the role of CHD7 in neural crest cell guidance and the regulation of mesenchymal-epithelial transition is unknown. Therefore, we undertook a genome-wide microarray expression analysis on wild-type and CHD7 deficient (Chd7Whi/+ and Chd7Whi/Whi) mouse embryos at day 9.5, the time point of neural crest cell migration. We identified 98 genes showing greater than two fold differences in expression (log2 fold-change) and a P-value to false discovery rate (FDR) < 0.05 between wild-type and Chd7Whi/Whi embryos. Interestingly, many misregulated genes are involved in neural crest cell and axon guidance like semaphorins and ephrin receptors. By performing knockdown experiments for Chd7 and one of its target genes, namely semaphorin3a in Xenopus laevis embryos, we could show abnormalities in the migration of neural crest cells in vivo. Additionally, we detected non-synonymous SEMA3A variations in 3 out of 45 CHD7 negative CHARGE patients suggesting a role for SEMA3A in the pathogenesis of CHARGE syndrome.
2014-07-01 | GSE46591 | GEO
Project description:CHD7 encodes an ATP-dependent chromatin remodeling factor. Mutation of this gene causes multiple developmental disorders including CHARGE syndrome, in which conotruncal anomalies are the most prevalent form of heart defects. How CHD7 regulates conotruncal development remains unclear. In this study, we establish that deletion of Chd7 in neural crest cells (NCCs) causes severe conotruncal defects and perinatal lethality. We thus provide the first mouse genetic evidence demonstrating that CHD7 cell-autonomously regulates cardiac NCC development, thereby clarifying a long-standing controversy in the literature. Using transcriptomic analyses, we show that CHD7 fine-tunes the expression of a gene network that is critical for cardiac NCC development. To gain further molecular insights into gene regulation by CHD7, we performed a protein-protein interaction screen by incubating recombinant CHD7 on a protein array. We find that CHD7 directly interacts with several developmental disorder-mutated proteins including WDR5, a core component of H3K4 methyltransferase complexes. This direct interaction suggested that CHD7 may recruit histone modifying enzymes to target loci, independently of its remodeling functions. We therefore generated a mouse model that harbors an ATPase-deficient allele and demonstrate that mutant CHD7 retains the ability to recruit H3K4 methyltransferase activity to its targets. Thus, our data uncover that CHD7 regulates cardiovascular development through ATP-dependent and -independent activities, shedding light on the etiology of CHD7-related congenital disorders. Importantly, our data also imply that patients carrying a premature stop codon versus missense mutations will likely display different molecular alterations; these patients might therefore require personalized therapeutic interventions.
2024-12-31 | GSE149860 | GEO
Project description:We isolated cardiac neural crest cells from E10.5 embryos and performed CHD7- and H3K27ac- ChIP-Seq. From this study, we determined the localization of CHD7 and H3K27ac along the chromosomes in cardiac nerual crest cells.
2024-12-31 | GSE149855 | GEO
Project description:Chromatin remodelling provides a key mechanism for the regulation of gene expression through dynamic alterations in nucleosome occupancy at promoters and enhancers. Haploinsufficiency for the ATP-dependent chromatin remodeller chromodomain-helicase-DNA-binding protein 7 (CHD7) causes human CHARGE syndrome. CHARGE is characterised by a distinct pattern of congenital anomalies, including cardiovascular malformations, and has traditionally been considered a neurocristopathy. We present a new perspective, by showing severe structural cardiovascular defects following ablation of Chd7 in the anterior mesoderm and other cardiac-related lineages. We identify multiple downstream pathways affected by the loss of Chd7 and disruption of excitation-contraction coupling in cardiomyocytes. Furthermore, we demonstrate CHD7 binding at the Sema3C promoter and alterations to the local chromatin structure in vivo, indicating direct transcriptional regulation. This work therefore provides novel insights into the etiology of heart defects arising in CHARGE syndrome and reveals a requirement for CHD7 activity in mesodermal cardiac progenitors.
2015-06-30 | GSE59963 | GEO