CHD7 specifies stem cell identity and neurogenic potential in neural progenitors by regulating SOX21 and BRN2 expression in human central nervous system
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE89951 | GEO | 2018/03/28
REPOSITORIES: GEO
Similar Datasets
Project description:CHARGE syndrome is a congenital disorder caused by mutations in Chromodomain Helicase DNA-binding domain 7 (CHD7) gene. We generated a cell line carrying HA-tag knock-in into the human CHD7 locus, mediated by CRISPR-Cas9 system. We then performed ChIP against HA antibody using the validated knock-in cells and subsequent high-throughput sequencing analysis.
2018-03-28 | GSE108506 | GEO
Project description:We performed ATAC-seq to profile the open chromatin lanscape in primary Chd7 WT and mutant GNPs. By analyzing the differentiate peaks between WT and mutant, we identified Chd7-dependent maintance of open chromatin at many neuronal genes.
2017-01-20 | GSE76984 | GEO
Project description:We identified genes that are regulated by Chd7 in GNPs
2017-01-20 | GSE72207 | GEO
Project description:One of the first steps in neurogenesis is the diversification of cells along the dorsoventral axis. In Drosophila the central nervous system develops from three longitudinal columns of cells: ventral cells that express the vnd/nk2 homeobox gene, intermediate cells, and dorsal cells that express the msh homeobox gene. Here we describe a new Drosophila homeobox gene, intermediate neuroblasts defective (ind), which is expressed specifically in the intermediate column cells. ind is essential for intermediate column development: Null mutants have a transformation of intermediate to dorsal column neuroectoderm fate, and only 10% of the intermediate column neuroblasts develop. The establishment of dorsoventral column identity involves negative regulation: Vnd represses ind in the ventral column, whereas ind represses msh in the intermediate column. Vertebrate genes closely related to vnd (Nkx2.1 and Nkx2.2), ind (Gsh1 and Gsh2), and msh (Msx1 and Msx3) are expressed in corresponding ventral, intermediate, and dorsal domains during vertebrate neurogenesis, raising the possibility that dorsoventral patterning within the central nervous system is evolutionarily conserved.
| S-EPMC317240 | biostudies-literature
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: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:Multiple congenital disorders often present complex phenotypes, but how the mutation of individual genetic factors can lead to multiple defects remains poorly understood. In the present study, we used human neuroepithelial (NE) cells and CHARGE patient-derived cells as an in vitro model system to identify the function of chromodomain helicase DNA-binding 7 (CHD7) in NE-neural crest bifurcation, thus revealing an etiological link between the central nervous system (CNS) and craniofacial anomalies observed in CHARGE syndrome. We found that CHD7 is required for epigenetic activation of superenhancers and CNS-specific enhancers, which support the maintenance of the NE and CNS lineage identities. Furthermore, we found that BRN2 and SOX21 are downstream effectors of CHD7, which shapes cellular identities by enhancing a CNS-specific cellular program and indirectly repressing non-CNS-specific cellular programs. Based on our results, CHD7, through its interactions with superenhancer elements, acts as a regulatory hub in the orchestration of the spatiotemporal dynamics of transcription factors to regulate NE and CNS lineage identities.
| S-EPMC5830929 | biostudies-literature
Project description:The role of CHD7 in human central nervous system development (ChIP-Seq)
| PRJNA427521 | ENA
Project description:Mutations in the chromatin remodeller CHD7 cause CHARGE syndrome (CS). Importantly, children with CS exhibit moderate to severe neurological and behaviour symptoms including autism. However, the neural substrates underlying these symptoms remain largely unknown. Here we show that zebrafish chd7 mutant display a nighttime hyperactivity behavioural phenotype and exhibit altered number and positioning of GABAergic neurons in brain regions. Using a transcriptomic approach, we identified many genes involved in cell adhesion, migration and receptor signalling that are dysregulated in the chd7 brain. We also show an abnomal hyperactivation of ERK signalling contributing to the GABAergic defects. A phenotype-based screen of 3850 compounds identifies a lead compound, ephedrine that ameliorates GABAergic and behavioural anomalies in chd7 animals. Our study identifies CHD7 as critical regulator of GABAergic network development. Importantly, we provide novel insight into the mechanisms underlying the neurological deficits in CS and identify a new therapeutic for CS-associated neurobehavioural symptoms.
2019-10-31 | GSE139623 | GEO
Project description:Chromatin remodeler CHD7 regulates the stem cell identity of human neural progenitors
| PRJNA436617 | ENA