Genome-wide analysis of CHD7 binding sites in cardiac progenitor cells [CUT&RUN]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE229628 | GEO | 2023/04/29
REPOSITORIES: GEO
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Project description:Chromodomain helicase DNA-binding protein 7 (Chd7) encodes an ATP-dependent chromatin remodeler required for normal human development. De novo mutations in CHD7 are the major cause of CHARGE syndrome which features multiple developmental defects. Previous studies have shown that CHD7 targets to specific genomic loci and alters local transcription potentially by remodeling the chromatin structure in a cell stage and lineage specific manner. We examined whether nuclear RNAs might contribute to its targeting and function. We used PAR-CLIP to identify a lncRNA, HERVH, that is uniquely expressed in pluripotent stem cells and preferentially interacts with CHD7. Knockdown of HERVH using LNAs or knockout of an individual copy of HERVH by CRISPR-Cas9 both resulted in increased binding of CHD7 and increased levels of H3K27ac at a subset of enhancers. Depletion of HERVH led to the activation of multiple genes, several of which might potentially poise cells towards differentiation. CHD7 bound HERVH RNA with high affinity but low specificity and that this interaction decreased the ability of CHD7 to bind and remodel nucleosomes. We present a model in which HERVH acts as a decoy to modulate the dynamics of CHD7 binding to enhancers in pluripotent cells and to prevent the activation of differentiation specific genes.
2021-10-10 | GSE171136 | GEO
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: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:Chromodomain helicase DNA-binding protein 7 (CHD7) is an ATP-dependent chromatin remodeling enzyme, functioning as chromatin reader to conduct epigenetic modification. Its effect on osteogenic differentiation of human dental follicle cells (hDFCs) remains unclear. Here we show CHD7 expression increases with osteogenic differentiation. knockdown of CHD7 impairs the osteogenic ability of hDFCs, characterized by reduced alkaline phosphatase activity and mineralization, and decreased expression of osteogenesis-related genes. Conversely, CHD7 overexpression enhances the osteogenic differentiation of hDFCs. Mechanically, RNA-seq analyses revealed the down-regulated enrichment of PTH (parathyroid hormone)/PTH1R (parathyroid hormone receptor-1) signaling pathway after CHD7 knockdown. We found the expression of PTH1R positively correlates with CHD7. Importantly, overexpression of PTH1R in CHD7-knockdown hDFCs partially rescued the impaired osteogenic differentiation. Our research demonstrates that CHD7 regulates the osteogenic differentiation of hDFCs by regulating the transcription of PTH1R.
2020-07-22 | GSE154822 | GEO
Project description:Chromodomain helicase DNA-binding protein 7 (Chd7) encodes an ATP-dependent chromatin remodeler required for normal human development. De novo mutations in CHD7 are the major cause of CHARGE syndrome which features multiple developmental defects. Previous studies have shown that CHD7 targets to specific genomic loci and alters local transcription potentially by remodeling the chromatin structure in a cell stage and lineage specific manner. We examined whether nuclear RNAs might contribute to its targeting and function. We used PAR-CLIP to identify a lncRNA, HERVH, that is uniquely expressed in pluripotent stem cells and preferentially interacts with CHD7. Knockdown of HERVH using LNAs or knockout of an individual copy of HERVH by CRISPR-Cas9 both resulted in increased binding of CHD7 and increased levels of H3K27ac at a subset of enhancers. Depletion of HERVH led to the activation of multiple genes, several of which might potentially poise cells towards differentiation. CHD7 bound HERVH RNA with high affinity but low specificity and that this interaction decreased the ability of CHD7 to bind and remodel nucleosomes. We present a model in which HERVH acts as a decoy to modulate the dynamics of CHD7 binding to enhancers in pluripotent cells and to prevent the activation of differentiation specific genes.
2021-10-10 | GSE171138 | GEO
Project description:Chromodomain helicase DNA-binding protein 7 (Chd7) encodes an ATP-dependent chromatin remodeler required for normal human development. De novo mutations in CHD7 are the major cause of CHARGE syndrome which features multiple developmental defects. Previous studies have shown that CHD7 targets to specific genomic loci and alters local transcription potentially by remodeling the chromatin structure in a cell stage and lineage specific manner. We examined whether nuclear RNAs might contribute to its targeting and function. We used PAR-CLIP to identify a lncRNA, HERVH, that is uniquely expressed in pluripotent stem cells and preferentially interacts with CHD7. Knockdown of HERVH using LNAs or knockout of an individual copy of HERVH by CRISPR-Cas9 both resulted in increased binding of CHD7 and increased levels of H3K27ac at a subset of enhancers. Depletion of HERVH led to the activation of multiple genes, several of which might potentially poise cells towards differentiation. CHD7 bound HERVH RNA with high affinity but low specificity and that this interaction decreased the ability of CHD7 to bind and remodel nucleosomes. We present a model in which HERVH acts as a decoy to modulate the dynamics of CHD7 binding to enhancers in pluripotent cells and to prevent the activation of differentiation specific genes.
2021-10-10 | GSE171137 | GEO
Project description:Chromodomain helicase DNA-binding protein 7 (Chd7) encodes an ATP-dependent chromatin remodeler required for normal human development. De novo mutations in CHD7 are the major cause of CHARGE syndrome which features multiple developmental defects. Previous studies have shown that CHD7 targets to specific genomic loci and alters local transcription potentially by remodeling the chromatin structure in a cell stage and lineage specific manner. We examined whether nuclear RNAs might contribute to its targeting and function. We used PAR-CLIP to identify a lncRNA, HERVH, that is uniquely expressed in pluripotent stem cells and preferentially interacts with CHD7. Knockdown of HERVH using LNAs or knockout of an individual copy of HERVH by CRISPR-Cas9 both resulted in increased binding of CHD7 and increased levels of H3K27ac at a subset of enhancers. Depletion of HERVH led to the activation of multiple genes, several of which might potentially poise cells towards differentiation. CHD7 bound HERVH RNA with high affinity but low specificity and that this interaction decreased the ability of CHD7 to bind and remodel nucleosomes. We present a model in which HERVH acts as a decoy to modulate the dynamics of CHD7 binding to enhancers in pluripotent cells and to prevent the activation of differentiation specific genes.
2021-10-10 | GSE171135 | GEO
Project description:Hematopoietic stem and progenitor cell (HSPC) formation and lineage differentiation involve gene expression programs orchestrated by transcription factors and epigenetic regulators. Knockdown of the chromatin remodeler chromodomain-helicase-DNA-binding protein 7 (CHD7) expanded phenotypic HSPCs, erythroid, and myeloid lineages in zebrafish and mouse embryos. CHD7 acts to suppress hematopoietic differentiation in a cell autonomous manner in the embryo and adult. CHD7 chromatin immunoprecipitation in human CD34+ and mouse HSPCs revealed enrichment of binding motifs for hematopoietic transcription factors including Runx1 and GATA factors, and decreased Runx1 occupancy correlated with loss of CHD7 occupancy. CHD7 physically interacts with Runx1 and suppresses Runx1-induced expansion of HSPCs during development, providing both physical and genetic evidence for the Runx1-CHD7 interaction. CHD7 modulates Runx1 activity to provide proper timing and function of HSPCs as they emerge during hematopoietic development or mature in adults, representing a distinct and evolutionarily conserved control mechanism to ensure accurate hematopoietic lineage differentiation. We profiled expression of CHD7 wild-type and deficient adult mice bone marrow long-term hematopoietic stem cells and found genes from several hematopoietic lineages are upregulated.
2018-07-01 | GSE84136 | GEO
Project description:Hematopoietic stem and progenitor cell (HSPC) formation and lineage differentiation involve gene expression programs orchestrated by transcription factors and epigenetic regulators. Knockdown of the chromatin remodeler chromodomain-helicase-DNA-binding protein 7 (CHD7) expanded phenotypic HSPCs, erythroid, and myeloid lineages in zebrafish and mouse embryos. CHD7 acts to suppress hematopoietic differentiation in a cell autonomous manner in the embryo and adult. We performed ChIP sequencing to determine the genomic localization of CHD7 in human CD34+ and mouse HSPCs, revealing enrichment of binding motifs for hematopoietic transcription factors including Runx1 and GATA factors. CHD7 occupied regions are transcriptionally active and are near genes with hematopoietic function. Decreased Runx1 occupancy correlated with loss of CHD7 occupancy. Together, the physical and genetic interaction data support a model in which CHD7 interacts with and modulates Runx1 activity to provide proper timing and function of HSPCs as they emerge during hematopoietic development or mature in adults. This represents a distinct and evolutionarily conserved control mechanism to ensure accurate hematopoietic lineage differentiation.
2019-07-27 | GSE83956 | GEO