Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA148637 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Emerging 3D genome mapping efforts suggest complex chromosomal folding structures. However, the true multiplex nature of chromatin interactions has yet to be fully explored. Here, we describe a chromatin interaction analysis by droplet-based sequencing (ChIA-Drop). In ChIA-Drop, individual chromatin complexes are partitioned into droplets that contain a gel bead of DNA-barcoded primers, such that tethered chromatin DNA fragments are uniquely indexed and amplified for sequencing and mapping to demarcate multiplex chromatin contacts. Thus, ChIA-Drop can identify complex chromatin interactions with unprecedented single-molecule precision, which is not possible using methods that analyze pairwise contacts via proximity ligation. We demonstrate that multiplex chromatin interactions predominantly contribute to topologically associated domains with high heterogeneity, and that multivalent promoter-centered interactions provide a topological model for gene transcription.
2019-02-11 | GSE109355 | GEO
Project description:Higher-order chromosomal organization for transcription regulation is poorly understood in eukaryotes. Using genome-wide Chromatin Interaction Analysis with Paired-End-Tag sequencing (ChIA-PET), we mapped long-range chromatin interactions associated with RNA polymerase II in human cells and uncovered widespread promoter-centered intragenic, extragenic, and intergenic interactions. These interactions further aggregated into higher-order clusters, wherein proximal and distal genes were engaged through promoter-promoter interactions. Most genes with promoter-promoter interactions were active and transcribed cooperatively, and some interacting promoters could influence each other implying combinatorial complexity of transcriptional controls. Comparative analyses of different cell lines showed that cell-specific chromatin interactions could provide structural frameworks for cell-specific transcription, and suggested significant enrichment of enhancer-promoter interactions for cell-specific functions. Furthermore, genetically-identified disease-associated noncoding elements were found to be spatially engaged with corresponding genes through long-range interactions. Overall, our study provides insights into transcription regulation by three-dimensional chromatin interactions for both housekeeping and cell-specific genes in human cells.
2012-01-20 | GSE33664 | GEO
Project description:Higher-order chromosomal organization for transcription regulation is poorly understood in eukaryotes. Using genome-wide Chromatin Interaction Analysis with Paired-End-Tag sequencing (ChIA-PET), we mapped long-range chromatin interactions associated with RNA polymerase II in human cells and uncovered widespread promoter-centered intragenic, extragenic, and intergenic interactions. These interactions further aggregated into higher-order clusters, wherein proximal and distal genes were engaged through promoter-promoter interactions. Most genes with promoter-promoter interactions were active and transcribed cooperatively, and some interacting promoters could influence each other implying combinatorial complexity of transcriptional controls. Comparative analyses of different cell lines showed that cell-specific chromatin interactions could provide structural frameworks for cell-specific transcription, and suggested significant enrichment of enhancer-promoter interactions for cell-specific functions. Furthermore, genetically-identified disease-associated noncoding elements were found to be spatially engaged with corresponding genes through long-range interactions. Overall, our study provides insights into transcription regulation by three-dimensional chromatin interactions for both housekeeping and cell-specific genes in human cells. RNA polymerase II (RNAPII) bound chromatin interactions were extracted with Chromatin Interaction Analysis with Paired-End Tag (ChIA-PET) sequencing, in order to study the transcription regulations with RNAPII-associated long-range chromatin interactions. Five cell lines, namely MCF7 (ATCC# HTB-22), K562 (ATCC# CCL-243), HCT116 (ATCC# CCL-247), HeLa (ATCC# CCL-2.2), and NB4 (Roussel and Lanotte, 2001) (provided by Dr. Sherman Weissman, Yale University), were grown under standard culture conditions and harvested at log phase. Harvested cells were cross-linked using 1% formaldehyde followed by neutralization with 0.2M glycine. Chromatin was isolated and subjected to ChIA-PET protocol as described in Fullwood et al (Fullwood et al: An oestrogen-receptor-alpha-bound human chromatin interactome. Nature 2009, 462(7269):58-64). The ChIA-PET sequence reads were processed and analyzed using ChIA-PET Tool (Li et al: ChIA-PET tool for comprehensive chromatin interaction analysis with paired-end tag sequencing. Genome Biol 2010, 11(2):R22).
2012-01-20 | E-GEOD-33664 | biostudies-arrayexpress
Project description:Using genome-wide Chromatin Interaction Analysis with Paired-End-Tag sequencing, we mapped long-range chromatin interactions associated with RNA polymerase II in three different mouse cell lines and uncovered widespread promoter-centered interactions. These interactions further aggregated into higher-order clusters, in which proximal and distant genes are engaged through enhancer-promoter interactions. Comparative analyses of different cell lines imply that cell specific enhancer interactions are dynamic among different cell specific transcription, and suggest significant enrichment of enhancer-promoter interactions for cell specific manner. Overall, our study provides novel insights into the three-dimensional basis of transcription activity in mouse cells. RNA polymerase II (RNAPII) guided chromatin interactions were discovered by Chromatin Interaction Analysis with Paired-End Tag (ChIA-PET) sequencing, in order to study genome-wise the enhancer-promoter interactions. Three cell lines, namely mouse embryonic stem cell E14, Neural stem cell NS5 and neuroshpere cells were grown under standard culture conditions and harvested at log phase. Harvested cells were cross-linked using 1% formaldehyde followed by neutralization with 0.2M glycine. Chromatin was isolated and subjected to ChIA-PET protocol as described in Fullwood et al, 2009. The ChIA-PET sequence reads were processed and analyzed using ChIA-PET Tool (Li et al, 2010)
2013-11-04 | E-GEOD-44067 | biostudies-arrayexpress
Project description:Understanding the topological configurations of chromatin can reveal valuable insights into how the genome and epigenome act in concert to control cell fate during development. Here we generate high-resolution architecture maps across seven genomic loci in embryonic stem cells and neural progenitor cells. We observe a hierarchy of 3-D interactions that undergo marked reorganization at the sub-Mb scale during differentiation. Distinct combinations of CTCF, Mediator, and cohesin show widespread enrichment in architecture at different length scales. CTCF/cohesin anchor long-range constitutive interactions that might form the topological basis for invariant sub-domains. Conversely, Mediator/cohesin together with pioneer factors bridge short-range enhancer-promoter interactions within and between larger sub-domains. Knockdown of Smc1 or Med12 in ES cells results in disruption of spatial architecture and down-regulation of genes found in cohesin-mediated interactions. We conclude that cell type-specific chromatin organization occurs at the sub-Mb scale and that architectural proteins shape the genome in hierarchical length scales. Analysis of higher-order chromatin chromatin architecture in mouse ES cells and ES-derived NPCs. Analysis of CTCF and Smc1 occupied sites in ES-derived NPCs.
2013-05-24 | E-GEOD-36203 | biostudies-arrayexpress
Project description:Understanding the topological configurations of chromatin can reveal valuable insights into how the genome and epigenome act in concert to control cell fate during development. Here we generate high-resolution architecture maps across seven genomic loci in embryonic stem cells and neural progenitor cells. We observe a hierarchy of 3-D interactions that undergo marked reorganization at the sub-Mb scale during differentiation. Distinct combinations of CTCF, Mediator, and cohesin show widespread enrichment in architecture at different length scales. CTCF/cohesin anchor long-range constitutive interactions that might form the topological basis for invariant sub-domains. Conversely, Mediator/cohesin together with pioneer factors bridge short-range enhancer-promoter interactions within and between larger sub-domains. Knockdown of Smc1 or Med12 in ES cells results in disruption of spatial architecture and down-regulation of genes found in cohesin-mediated interactions. We conclude that cell type-specific chromatin organization occurs at the sub-Mb scale and that architectural proteins shape the genome in hierarchical length scales.
2013-05-24 | GSE36203 | GEO
Project description:A large number of genetic variants associated with human diseases are found in non-coding DNA and may contribute to illness by affecting gene regulation, but mechanistic study of these variants has been hindered by a lack of information of their potential regulatory targets. In order to overcome this limitation, we generate maps of long-range chromatin interactions centered on 19,539 promoters in 27 human cell/tissue types, and use this information to infer putative target genes of candidate cis-regulatory sequences throughout the human genome. In additional to known enhancer-promoter interactions, we also confirm widespread promoter-promoter interactions and obtain evidence suggesting enhancer-like function for many promoter regions. These promoter-centered chromatin interaction maps corroborate target genes of genetic variants defined in previous genome-wide association studies, predict new target genes of many disease-associated genetic variants, and contribute novel insights into a broad spectrum of human traits and diseases.
2019-07-31 | GSE86189 | GEO
Project description:Chromosome conformation capture technologies have revealed important insights into genome folding. Yet, how spatial genome architecture is related to gene expression and cell fate remains unclear. We mapped comprehensively 3D chromatin organization during mouse neural differentiation in vitro and in vivo, generating the highest resolution Hi-C maps available to date. We found that transcription is correlated with chromatin insulation and long-range interactions, but dCas9-mediated activation is insufficient for creating topological domain (TAD) boundaries de novo. Additionally, we discovered long-range contacts between gene bodies of exon-rich, active genes in all cell types. During neural differentiation, contacts between active TADs become less pronounced while inactive TADs interact stronger. An extensive Polycomb network in stem cells is disrupted, while dynamic interactions between proneural transcription factors appear in vivo. Finally, cell-type specific enhancer-promoter contacts are established concomitant to gene expression. This work shows that multiple factors influence the dynamics of chromatin interactions in development.
2017-10-18 | GSE96107 | GEO
Project description:Recent studies of genome-wide chromatin interactions have revealed that the human genome is partitioned into many self-associating topological domains. The boundary sequences are enriched for binding sites of CTCF and the cohesin complex, implicating these two factors in the establishment or maintenance of topological domains. To determine the role of cohesin and CTCF in higher order chromatin architecture in human cells, we proteolytically cleaved the cohesin complex from interphase chromatin and examined changes in chromosomal organization as well as transcriptome. We observed a general loss of local chromosomal interactions upon disruption of cohesin complex, but the topological domains remain intact. However, we found that depletion of CTCF by RNA interference in these cells not only reduced intra-domain interactions but also increased inter-domain interactions. Further more, distinct groups of genes become mis-regulated upon depletion of cohesin and CTCF. Taken together, these observations suggest that CTCF and cohesin contribute in different ways to chromatin organization and gene regulation. Hi-C and mRNA-seq experiments in Cohesin and CTCF depleted HEK293 cells
2013-12-16 | E-GEOD-44267 | biostudies-arrayexpress
Project description:Eya1 is critical for specifying and maintaining nephron progenitor cells (NPCs). It belongs to a protein family known as phosphatase-transcriptional activator but without intrinsic DNA-binding activity. However, the Eya1-centered network and the spectrum of its interaction partners are underexplored. Here, we combined transcriptomic, genomic and proteomic approaches to characterize gene regulation by Eya1 in the NPCs. We identified Eya1 target genes, genomic binding sites, and partner proteins. Eya1 binds preferentially to promoter sequences and interacts with general transcription factors (TFs), RNA polymerases, different types of TFs, and DNA replication/repair proteins. Intriguingly, we identified REST-binding motifs in 76% of Eya1-binding sites without H3K27ac-deposition, which were present in many Eya1 target genes upregulated in Eya1-deficient NPCs. Eya1 copurified REST-interacting proteins, including chromatin-remodeling factors with ATPase or helicase activity, histone deacetylase/lysine demethylase, and corepressors. Coimmunoprecipitation validated complex formation between Eya1, Hdac1 and Cdyl in kidneys. Thus, these results suggest that through interactions with chromatin-remodeling factors, Eya1 may modify chromatin structure to facilitate the assembly of regulatory complexes that regulate transcription positively or negatively. These findings provide a mechanistic basis for how Eya1 functions as a multifunction protein by cooperating with protein partners in various fundamental biological processes to maintain the cellular state of NPCs.
2022-10-19 | GSE202956 | GEO