Chromosome Compartments on the Inactive X Guide TAD Formation Independently of Transcription during X-Reactivation
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ABSTRACT:
PROVIDER: PRJNA661320 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12584300_1.fastq.gz | Fastqsanger.gz | |||
| SRR12584300_2.fastq.gz | Fastqsanger.gz | |||
| SRR12584400_1.fastq.gz | Fastqsanger.gz | |||
| SRR12584400_2.fastq.gz | Fastqsanger.gz | |||
| SRR12584301_1.fastq.gz | Fastqsanger.gz |
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Project description:A hallmark of chromosome organization is the partition into transcriptionally active A and repressed B compartments, and into topologically associating domains (TADs). Both structures were regarded to be absent from the inactive mouse X chromosome, but to be re-established with transcriptional reactivation and chromatin opening during X-reactivation. Here, we combine a tailor-made mouse iPSC reprogramming system and high-resolution Hi-C to produce a time course combining gene reactivation, chromatin opening and chromosome topology during X-reactivation. Contrary to previous observations, we observe A/B-like compartments on the inactive X harbouring multiple subcompartments. While partial X-reactivation initiates within a compartment rich in X-inactivation escapees, it then occurs rapidly along the chromosome, concomitant with downregulation of Xist. Importantly, we find that TAD formation precedes transcription and initiates from Xist-poor compartments. Here, we show that TAD formation and transcriptional reactivation are causally independent during X-reactivation while establishing Xist as a common denominator.
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Project description:To investigate the dynamics of X-chromosome reactivation, we differentiated mouse embryonic stem cells (ESCs) into neural precursor cells (NPCs) and later reprogrammed them into induced pluripotent stem cells (iPSCs). During the conversions of NPCs into iPSC, we assessed the kinetics of X-chromosome reactivation. We generated allele-specific RNA-seq datasets to assess gene reactivation dynamics, employed ATAC-seq to investigate chromatin opening dynamics and performed in situ Hi-C to explore dynamics of chromosome structure.
2021-04-02 | GSE157448 | GEO
Project description:Detailed genomic contact maps have revealed that chromosomes are composed of developmentally stable topologically associated domains (TADs) and more flexible sub-TADs. These domains reside in active and inactive nuclear compartments, but cause and consequence of compartmentalization are largely unknown. Here, we combined lacO/lacR binding platforms with allele-specific 4C technologies to track their precise position in the three-dimensional genome upon recruitment of NANOG, SUV39H1 or EZH2. We observed locked genomic loci resistant to spatial repositioning and unlocked loci that could be repositioned to different nuclear sub-compartments with distinct chromatin signatures. Focal protein recruitment caused the entire sub- TAD, but not surrounding regions, to engage in new genomic contacts. Compartment switching was uncoupled from gene expression changes and enzymatically modifying histones per se was insufficient for repositioning. Collectively this suggests that transassociated factors determine three-dimensional compartmentalization independent of their cis-effect on local chromatin composition and activity. 4C-seq was performed on a range of viewpoints in 129/Sv;C57BL/6 embryonic stem cells carying a lacO array in chromosome 8 and 11.
2015-12-19 | E-GEOD-76174 | biostudies-arrayexpress
Project description:The non-canonical SMC protein SmcHD1 antagonises TAD formation on the inactive X chromosome
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Project description:Detailed genomic contact maps have revealed that chromosomes are composed of developmentally stable topologically associated domains (TADs) and more flexible sub-TADs. These domains reside in active and inactive nuclear compartments, but cause and consequence of compartmentalization are largely unknown. Here, we combined lacO/lacR binding platforms with allele-specific 4C technologies to track their precise position in the three-dimensional genome upon recruitment of NANOG, SUV39H1 or EZH2. We observed locked genomic loci resistant to spatial repositioning and unlocked loci that could be repositioned to different nuclear sub-compartments with distinct chromatin signatures. Focal protein recruitment caused the entire sub- TAD, but not surrounding regions, to engage in new genomic contacts. Compartment switching was uncoupled from gene expression changes and enzymatically modifying histones per se was insufficient for repositioning. Collectively this suggests that transassociated factors determine three-dimensional compartmentalization independent of their cis-effect on local chromatin composition and activity.
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Project description:Topologically Associating Domains (TADs) have been proposed to both guide and constrain enhancer activity. Shh is located within a TAD known to contain all its enhancers. To investigate the importance of chromatin conformation and TAD integrity on developmental gene regulation, we have manipulated the Shh TAD – creating internal deletions, deleting CTCF sites, and deleting and inverting sequences at TAD boundaries. Chromosome conformation capture and fluorescence in situ hybridisation assays were used to investigate the changes in chromatin conformation that result from these manipulations. Our data suggest that these substantial alterations in TAD structure has no readily detectable effect on Shh expression patterns during development – except where enhancers are deleted - and results in no detectable phenotypes. Only in the case of a larger deletion of one TAD boundary could ectopic influence of the Shh limb enhancer be detected on a gene (Mnx1) in the neighbouring TAD. Our data suggests that, contrary to expectations, the developmental regulation of Shh expression is remarkably robust to TAD perturbations.
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Project description:The non-canonical SMC protein SmcHD1 antagonises TAD formation on the inactive X chromosome (Repli-seq)
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Project description:Genome organization is driven by forces affecting transcriptional state, but the relationship between transcription and genome architecture remains unclear. Here, we identified the Drosophila transcription factor Motif 1 Binding Protein (M1BP) in physical association with the gypsy chromatin insulator core complex, including the universal insulator protein CP190. M1BP is required for enhancer-blocking and barrier activities of the gypsy insulator as well as its proper nuclear localization. Genome-wide, M1BP specifically colocalizes with CP190 at Motif 1-containing promoters, which are enriched at topologically associating domain (TAD) borders. M1BP facilitates CP190 chromatin binding at many shared sites and vice versa. Both factors promote Motif 1-dependent gene expression and transcription near TAD borders genome-wide. Finally, loss of M1BP reduces chromatin accessibility and increases both inter- and intra-TAD local genome compaction. Our results reveal physical and functional interaction between CP190 and M1BP to activate transcription at TAD borders and mediate chromatin insulator-dependent genome organization.
2021-06-07 | PXD026497 | Pride
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:X-chromosome inactivation (XCI) entails a massive structural reorganization of the inactive X (Xi). However the molecular architecture of the Xi is unknown. Here we show that the Xi lacks typical autosomal features such as active/inactive compartments and topologically associating domains (TADs), except around a small number of genes that escape XCI and remain expressed. Escaping genes form TADs and retain DNA accessibility at promoter-proximal and CTCF binding sites, indicating that these loci can avoid Xist-mediated erasure of chromosomal structure. We further show that genesilencing competent Xist RNA is sufficient to induce segregation of the Xi into two ‘mega-domains’ separated by a boundary that includes the DXZ4 macrosatellite. Deletion of this boundary prior to XCI results in fusion of the megadomains and altered patterns of escape that correlate with changes in TAD structure following differentiation and XCI . Our results suggest a critical role for the boundary locus and Xist RNA in shaping the structure of the Xi and modulating escape from XCI. Our findings also point to roles of transcription and CTCF binding in TAD formation in the context of facultative heterochromatin.
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