CHD7 targets active gene enhancer elements to modulate ES cell-specific gene expression.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE22341 | GEO | 2010/06/16
SECONDARY ACCESSION(S): PRJNA127519
REPOSITORIES: GEO
Similar Datasets
Project description:Gene expression changes were measured between mouse ES cells of three genotypes: WT Chd7, Heterzygous Chd7 Null, Homozygous Chd7 Null. The hypothesis being tested was that CHD7, a chromatin remodeling protein, functions as a transcriptional regulator. This experiment was performed to detect gene targets of CHD7-mediated regulation. We report the genome-wide binding profile of CHD7, the protein implicated in CHARGE syndrome, in mouse ES cells using ChIP-Seq technology. Combining these data with other genomic datasets, we discover CHD7 to colocalize with other transcription factors including Oct4, Nanog, Sox2, and p300 at gene enhancer elements to regulate ES cell specific gene expression. Chd7 wildtype, heterozygous, and homozygous ES cells derived from preimplantation embryos were grown on feeder cells and total RNA was isolated using Trizol. The ratio of ES to feeder cells was estimated at 5:1. ChIP sequencing of CHD7 and p300 in mouse ES cells
2010-06-15 | E-GEOD-22341 | biostudies-arrayexpress
Project description:CHD7 is a member of the chromodomain helicase DNA binding domain family of ATP-dependent chromatin remodeling enzymes. De novo mutation of the CHD7 gene is a major cause of CHARGE syndrome, a genetic disease characterized by a complex constellation of birth defects. To gain insight to the function of CHD7, we mapped the distribution of the CHD7 protein on chromatin using the approach of chromatin immunoprecipitation on tiled microarrays (ChIP-chip). These studies were performed in human colorectal carcinoma cells, human neuroblastoma cells, and mouse embryonic stem (ES) cells before and after differentiation into neural precursor cells. The results indicate that CHD7 localizes to discrete locations along chromatin that are specific to each cell type, and that the cell-specific binding of CHD7 correlates with a subset of histone H3 methylated at lysine 4 (H3K4me). The CHD7 sites change concomitantly with H3K4me patterns during ES cell differentiation, suggesting that H3K4me is part of the epigenetic signature that defines lineage-specific association of CHD7 with specific sites on chromatin. Furthermore, the CHD7 sites are predominantly located distal to transcription start sites, most often contained within DNase hypersensitive sites, frequently conserved, and near genes expressed at relatively high levels. These features are similar to those of gene enhancer elements, raising the possibility that CHD7 functions in enhancer mediated transcription, and that the congenital anomalies in CHARGE syndrome are due to alterations in transcription of tissue-specific genes normally regulated by CHD7 during development. ChIP-chip experiments were performed for CHD7 and H3K4 mono-,di-, and trimethylation modifications in 4 cells types: human DLD1 and SH-SY5Y; mouse ES and differentiated neural precursor cells derived from mouse ES cells. Microarrays used in these experiments tiled all or subset of ENCODE regions (in mouse, analogous ENCODE regions were assayed). At least two biological replicates were performed for each CHD7 ChIP experiment; H3K4 ChIP's were performed once in each cell type.
2009-01-22 | E-GEOD-14460 | biostudies-arrayexpress
Project description:CHD7 is a member of the chromodomain helicase DNA binding domain family of ATP-dependent chromatin remodeling enzymes. De novo mutation of the CHD7 gene is a major cause of CHARGE syndrome, a genetic disease characterized by a complex constellation of birth defects. To gain insight to the function of CHD7, we mapped the distribution of the CHD7 protein on chromatin using the approach of chromatin immunoprecipitation on tiled microarrays (ChIP-chip). These studies were performed in human colorectal carcinoma cells, human neuroblastoma cells, and mouse embryonic stem (ES) cells before and after differentiation into neural precursor cells. The results indicate that CHD7 localizes to discrete locations along chromatin that are specific to each cell type, and that the cell-specific binding of CHD7 correlates with a subset of histone H3 methylated at lysine 4 (H3K4me). The CHD7 sites change concomitantly with H3K4me patterns during ES cell differentiation, suggesting that H3K4me is part of the epigenetic signature that defines lineage-specific association of CHD7 with specific sites on chromatin. Furthermore, the CHD7 sites are predominantly located distal to transcription start sites, most often contained within DNase hypersensitive sites, frequently conserved, and near genes expressed at relatively high levels. These features are similar to those of gene enhancer elements, raising the possibility that CHD7 functions in enhancer mediated transcription, and that the congenital anomalies in CHARGE syndrome are due to alterations in transcription of tissue-specific genes normally regulated by CHD7 during development.
2009-01-23 | GSE14460 | GEO
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:CHD7, an ATP-dependent chromatin remodeler, is disrupted in CHARGE syndrome, an autosomal dominant condition characterized by variably penetrant abnormalities in craniofacial, cardiac, and neuronal tissues. The inner ear is uniquely sensitive to CHD7 levels and is the most commonly affected organ in individuals with CHARGE. Interestingly, up- or down-regulation of retinoic acid (RA) signaling during embryogenesis leads to developmental defects similar to those in CHARGE syndrome, suggesting CHD7 and RA share target genes or signaling pathways. Here, we report that CHD7 and retinoic acid receptor (RAR) do not directly interact, and that RA induces rapid neuronal differentiation of human SH-SY5Y neuroblastoma cells without affecting CHD7 levels. Instead, we provide evidence that CHD7 directly regulates expression of Aldh1a3, which encodes an RA synthetic enzyme, and that loss of Aldh1a3 partially rescues Chd7-mutant mouse inner ear defects, indicating that ALDH1A3 acts with CHD7 in a common genetic pathway to regulate inner ear development.
2020-08-30 | GSE103288 | GEO
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:Mutations in CHD7, encoding ATP-dependent chromodomain-helicase-DNA-binding protein 7, in CHARGE syndrome leads to multiple congenital anomalies including growth retardation, craniofacial malformations and neurological dysfunction. Currently, mechanisms underlying the CNS phenotypes remain poorly understood. Here, we show that Chd7 is a direct transcriptional target of oligodendrogenesis-promoting factors Olig2 and Brg1 and required for proper timing of CNS myelination and remyelination. Genome-occupancy analyses coupled with transcriptome profiling reveal that Chd7 cooperates with Sox10 to target the enhancers of key myelinogenic genes, and identify novel Chd7 target. Examination of Chd7 and Sox10 genomewide occupancy in differentiating oligodendrocytes
2016-02-29 | E-GEOD-72725 | biostudies-arrayexpress
Project description:CHARGE syndrome is a congenital disorder caused by mutations in Chromodomain Helicase DNA-binding domain 7 (CHD7) gene. We performed single cell RNA-seq analysis in CTRL and CHD7-knockdown lt-NES cells.
2018-03-28 | GSE108275 | 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:Regulation of chromatin plays fundamental roles in the normal development of the brain. Haploinsufficiency of the chromatin remodeling enzyme CHD7 causes CHARGE syndrome, a genetic disorder that prominently affects the development of the cerebellum. However, how CHD7 controls chromatin states in the cerebellum remains incompletely understood. Using conditional knockout of CHD7 in granule cell precursors in the mouse cerebellum, we find that CHD7 robustly promotes the accessibility and activity of enhancers in granule cell precursors. Remarkably, in vivo profiling of genome architecture reveals that CHD7 operates locally to stimulate enhancer activation, thereby driving the expression of topologically-interacting genes. Genome and gene ontology studies show that CHD7-regulated enhancers are associated prominently with genes that control brain tissue morphogenesis. Accordingly, conditional knockout of CHD7 triggers a striking phenotype of cerebellar polymicrogyria, which we have also found in a case of CHARGE syndrome. Finally, we uncover a CHD7-dependent switch in the preferred orientation of granule cell precursor division in the developing cerebellum, providing a cellular basis for the cerebellar polymicrogyria phenotype upon loss of CHD7. Collectively, our findings define CHD7 function in the regulation of the epigenome in granule cell precursors and identify a surprising link of CHD7 to the control of cerebellar cortical morphogenesis, with potential implications for our understanding of CHARGE syndrome.
2021-04-07 | GSE164360 | GEO