CHD7 marks TAD boundaries during neuronal differentiation [ChIP-Seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1244622 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32939129.fastq.gz | Fastqsanger.gz | |||
| SRR32939130.fastq.gz | Fastqsanger.gz | |||
| SRR32939131.fastq.gz | Fastqsanger.gz | |||
| SRR32939132.fastq.gz | Fastqsanger.gz | |||
| SRR32939133.fastq.gz | Fastqsanger.gz |
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Project description:The chromodomain helicase DNA binding protein 7 (CHD7) is a nucleosome repositioner implicated in multiple cellular processes, including neuronal differentiation. We identified CHD7 marked sites at TAD boundaries that regulate neuronal differentiation in an otic stem cell line. We showed that CHD7 co-occupied CTCF sites genome-wide. We identified CTCF+ CHD7+ sites near an essential transcription factor, Sox11, required for otic neuronal differentiation. The Sox11 promoter and 3’ untranslated region (UTR) showed CHD7 enrichment. The CHD7-marked sites at the 3’UTR displayed histone marks corresponding to active transcription that resulted in Sox11 antisense transcripts. Blocking the singular CHD7-marked site with CRISPRi decreased neurite lengths, reduced neuronal marker expression (TUBB3), and attenuated Sox11 antisense transcripts. Sox11 antisense transcripts were previously suggested to form double-stranded RNA and degrade the Sox11 transcript. Surprisingly, the level of the Sox11 sense transcripts remained unaffected after CRISPRi. We propose that CHD7 at TAD boundaries modulate the chromatin accessibility of CTCF-marked insulators, altering the 3D chromatin organization and ultimately affecting gene expression. Our results implicate a general mechanism of CHD7 in facilitating neuronal differentiation and provide insight into CHD7 dysfunction in CHARGE syndrome, an intellectual developmental disability disorder.
2025-04-07 | GSE293438 | GEO
Project description:The chromodomain helicase DNA binding protein 7 (CHD7) is a nucleosome repositioner implicated in multiple cellular processes, including neuronal differentiation. We identified CHD7 marked sites at TAD boundaries that regulate neuronal differentiation in an otic stem cell line. We showed that CHD7 co-occupied CTCF sites genome-wide. We identified CTCF+ CHD7+ sites near an essential transcription factor, Sox11, required for otic neuronal differentiation. The Sox11 promoter and 3’ untranslated region (UTR) showed CHD7 enrichment. The CHD7-marked sites at the 3’UTR displayed histone marks corresponding to active transcription that resulted in Sox11 antisense transcripts. Blocking the singular CHD7-marked site with CRISPRi decreased neurite lengths, reduced neuronal marker expression (TUBB3), and attenuated Sox11 antisense transcripts. Sox11 antisense transcripts were previously suggested to form double-stranded RNA and degrade the Sox11 transcript. Surprisingly, the level of the Sox11 sense transcripts remained unaffected after CRISPRi. We propose that CHD7 at TAD boundaries modulate the chromatin accessibility of CTCF-marked insulators, altering the 3D chromatin organization and ultimately affecting gene expression. Our results implicate a general mechanism of CHD7 in facilitating neuronal differentiation and provide insight into CHD7 dysfunction in CHARGE syndrome, an intellectual developmental disability disorder.
2025-04-07 | GSE293437 | GEO
Project description:The chromodomain helicase DNA binding protein 7 (CHD7) is a nucleosome repositioner implicated in multiple cellular processes, including neuronal differentiation. We identified CHD7 marked sites at TAD boundaries that regulate neuronal differentiation in an otic stem cell line. We showed that CHD7 co-occupied CTCF sites genome-wide. We identified CTCF+ CHD7+ sites near an essential transcription factor, Sox11, required for otic neuronal differentiation. The Sox11 promoter and 3’ untranslated region (UTR) showed CHD7 enrichment. The CHD7-marked sites at the 3’UTR displayed histone marks corresponding to active transcription that resulted in Sox11 antisense transcripts. Blocking the singular CHD7-marked site with CRISPRi decreased neurite lengths, reduced neuronal marker expression (TUBB3), and attenuated Sox11 antisense transcripts. Sox11 antisense transcripts were previously suggested to form double-stranded RNA and degrade the Sox11 transcript. Surprisingly, the level of the Sox11 sense transcripts remained unaffected after CRISPRi. We propose that CHD7 at TAD boundaries modulate the chromatin accessibility of CTCF-marked insulators, altering the 3D chromatin organization and ultimately affecting gene expression. Our results implicate a general mechanism of CHD7 in facilitating neuronal differentiation and provide insight into CHD7 dysfunction in CHARGE syndrome, an intellectual developmental disability disorder.
2025-04-07 | GSE293439 | GEO
Project description:CHD7 marks TAD boundaries during neuronal differentiation [RNA-Seq]
| PRJNA1244620 | ENA
Project description:CHD7 marks TAD boundaries during neuronal differentiation [Cut & Tag]
| PRJNA1244626 | ENA
Project description:The genome is partitioned into Topologically Associating Domains (TADs). About half of the boundaries of these TADs exhibit transcriptional activity and are correlated with better TAD insulation. However, the association between these transcripts and TAD insulation, enhancer:promoter interactions and transcription of genes remains unknown. Here we investigate the functional roles of these bRNAs (boundary-RNA) in boundary insulation and consequent effects on enhancer-promoter interactions and TAD transcription genome-wide and more specifically on the disease relevant INK4a/ARF TAD. Using a series of CTCF site deletions and bRNA knockdown experiments at this TAD boundary, we show a direct association of CTCF with the bidirectional bRNAs where the loss of bRNA triggers the concomitant loss of: CTCF at the TAD boundary, its insulation, enhancer:promoter interactions and gene transcription within the targeted TAD. We used another series of enhancer deletions and CRISPRi on promoters within INK4a/ARF TAD to better understand the regulation and origins of bRNA itself. We observe that the enhancers interact with boundaries and positively regulate the bRNA transcription at TAD boundaries. In return, the bRNAs recruit/stabilize the CTCF even on weak motifs within these boundaries and supports CTCF binding in clusters, therefore enhancing TAD insulation. This favors the intra-TAD enhancer:promoter interactions and leads to robust gene transcription. Functionally, bRNAs are more stable than eRNAs and their knockdown exactly mimics the CTCF site deletion. Furthermore, transcribing boundaries exhibit high TAD transcription in TCGA tumour datasets. Together, these results show that active enhancers directly mediate better insulation of TADs by activating the transcription at TAD boundaries triggering CTCF clustering at the boundary which results in better insulation and favours robust intra-TAD enhancer:promoter interactions to activate the gene transcription.
2022-12-28 | GSE180659 | GEO
Project description:Mammalian genome is hierarchically organized by CTCF and cohesin through loop extrusion mechanism to facilitate the organization of topologically associating domains (TADs). Mounting evidence suggests additional factors/mechanisms exist to orchestrate TAD formation and maintenance. In this study, we investigate the potential role of RNA binding proteins (RBPs) in TAD organization. By integrated analyses of global RBP binding and 3D genome mapping profiles from both K562 and HepG2 cells, our study unveils the prevalent enrichment of RBPs on TAD boundaries and define boundary associated RBPs (baRBPs). We found that baRBP binding is correlated with enhanced TAD insulation strength and in a CTCF independent manner. Moreover, baRBP binding is associated with nascent promoter transcription. Additional experimental testing was performed using RBFox2 as a paradigm. Knockdown of RBFox2 in K562 cells causes moderate TAD reorganization. Moreover, RBFox2 enrichment on TAD boundaries is a conserved phenomenon in C2C12 myoblast (MB) cells. RBFox2 is down-regulated and its bound boundaries are remodeled during MB differentiation into myotubes (MTs). Finally, transcriptional inhibition indeed decreases RBFox2 binding and disrupts TAD boundary insulation. Altogether, our findings demonstrate that RBPs can play active role in modulating TAD organization through co-transcriptional association and synergistic action with nascent promoter transcripts.
2025-02-12 | GSE277220 | GEO
Project description:Pervasive RNA Binding Protein Enrichment on TAD Boundaries Regulates TAD Organization
| PRJNA1018867 | ENA
Project description:Three-dimensional genome structure plays an important role in gene regulation. Globally chromosomes are organized into active and inactive compartments, while at the gene level looping interactions connect promoters to regulatory elements. Topologically Associating Domains (TADs), typically several hundred kilobases in size form an intermediate level of organization. Major questions include how TADs are formed and what their relation is with looping interactions between genes and regulatory elements. Here we performed a focused 5C analysis of a 2.8 Mb region on chromosome 7 surrounding CFTR in a panel of cell types. We find that the same TAD boundaries are present in all cell types, indicating that TADs represent a universal chromosome architecture. Further, we find that these TAD boundaries are present irrespective of expression and looping of genes located between them. In contrast looping interactions between promoters and regulatory elements are cell-type specific and occur mostly within TADs. This is exemplified by the CFTR promoter that in different cell types interacts with distinct sets of distal cell type-specific regulatory elements that are all located within the same TAD. Finally, we find that long-range associations between loci located in different TADs are also detected but these display much lower interaction frequencies than looping interactions within TADs. Interestingly, interactions between TADs are also highly cell type-specific and often involve loci clustered around TAD boundaries. These data point to key roles of invariant TAD boundaries in constraining as well as mediating cell type-specific long-range interactions and gene regulation. We investigated a 2.8 Mb region on Chromosome 7 (hg18 chr7: 115797757-118405450) containing the ENCODE region ENm001 42. The 5C experiment was designed to interrogate looping interactions between HindIII fragments containing transcription start sites (TSSs) and any other HindIII restriction fragment (distal fragments) in the target region. Libraries were generated for five cell lines: Caco2, Calu3, Capan1, GM12878 and HepG2, with two biological replicates for each line. 5C probes were designed at HindIII restriction sites (AAGCTT) using 5C primer design tools previously developed and made publicly available online at our My5C website (http://my5C.umassmed.edu). Probes were designed based on the ENCODE manual region 1 (ENM001) design 25 with additional probes placed throughout the region when appropriate. We also added probes to extend the analysis to include a 700 Kb gene desert region located directly adjacent to ENM001. Probe settings were: U-BLAST, 3; S-BLAST, 100; 15-MER, 3,000; MIN_FSIZE, 250; MAX_FSIZE, 20,000; OPT_TM, 65; OPT_PSIZE, 40. We designed 74 reverse 5C probes, and 605 forward 5C probes.
2016-01-07 | E-GEOD-75634 | biostudies-arrayexpress
Project description:Pervasive RNA Binding Protein Enrichment on TAD Boundaries Regulates TAD Organization [RNA-seq]
| PRJNA1161385 | ENA