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CTCF chromatin residence time controls 3D genome organization, gene expression and DNA methylation in pluripotent cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE154009 | GEO | 2021/06/04

REPOSITORIES: GEO

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CTCF chromatin residence time controls 3D genome organization, gene expression and DNA methylation in pluripotent cells [Hi-C]

Project description:The eleven zinc finger (ZF) protein CTCF regulates topologically associating domain (TAD) formation and transcription through selective binding to thousands of genomic sites. We replaced endogenous CTCF in mouse embryonic stem (ES) cells with GFP-tagged wildtype or mutant proteins lacking individual ZFs. We examined the various ES cell lines using next generation sequencing methods (ChIP-Seq, RNA-Seq, MedSeq, HiC) in order to identify additional determinants of CTCF positioning and function.

2021-06-04 | GSE153948 | GEO

CTCF chromatin residence time controls 3D genome organization, gene expression and DNA methylation in pluripotent cells [ChIP-Seq, RNA-seq, Med-Seq]

2021-06-04 | GSE154008 | GEO

CTCF chromatin residence time controls 3D genome organization, gene expression and DNA methylation in pluripotent cells

Project description:CTCF chromatin residence time controls 3D genome organization, gene expression and DNA methylation in pluripotent cells

| PRJNA644799 | ENA

CTCF chromatin residence time controls 3D genome organization, gene expression and DNA methylation in pluripotent cells [Hi-C]

Project description:CTCF chromatin residence time controls 3D genome organization, gene expression and DNA methylation in pluripotent cells [Hi-C]

| PRJNA644596 | ENA

DNA (de)methylation in embryonic stem cells controls CTCF-dependent chromatin boundaries.

Project description:Coordinated changes of DNA (de)methylation, nucleosome positioning, and chromatin binding of the architectural protein CTCF play an important role for establishing cell-type-specific chromatin states during differentiation. To elucidate molecular mechanisms that link these processes, we studied the perturbed DNA modification landscape in mouse embryonic stem cells (ESCs) carrying a double knockout (DKO) of the Tet1 and Tet2 dioxygenases. These enzymes are responsible for the conversion of 5-methylcytosine (5mC) into its hydroxymethylated (5hmC), formylated (5fC), or carboxylated (5caC) forms. We determined changes in nucleosome positioning, CTCF binding, DNA methylation, and gene expression in DKO ESCs and developed biophysical models to predict differential CTCF binding. Methylation-sensitive nucleosome repositioning accounted for a significant portion of CTCF binding loss in DKO ESCs, whereas unmethylated and nucleosome-depleted CpG islands were enriched for CTCF sites that remained occupied. A number of CTCF sites also displayed direct correlations with the CpG modification state: CTCF was preferentially lost from sites that were marked with 5hmC in wild-type (WT) cells but not from 5fC-enriched sites. In addition, we found that some CTCF sites can act as bifurcation points defining the differential methylation landscape. CTCF loss from such sites, for example, at promoters, boundaries of chromatin loops, and topologically associated domains (TADs), was correlated with DNA methylation/demethylation spreading and can be linked to down-regulation of neighboring genes. Our results reveal a hierarchical interplay between cytosine modifications, nucleosome positions, and DNA sequence that determines differential CTCF binding and regulates gene expression.

| S-EPMC6499307 | biostudies-literature

CTCF chromatin residence time controls 3D genome organization, gene expression and DNA methylation in pluripotent cells [ChIP-Seq, RNA-seq, Med-Seq]

Project description:CTCF chromatin residence time controls 3D genome organization, gene expression and DNA methylation in pluripotent cells [ChIP-Seq, RNA-seq, Med-Seq]

| PRJNA644803 | ENA

Is developmental synchrony enabled by CTCF residence time?

Project description:Depletion of CTCF in cultured cells has minor effects on transcription whereas its mutation leads to embryonic lethality and developmental defects. In a recent issue of Nature Cell Biology, Soochit et al. (2021) show that the residence time of CTCF on DNA may explain its critical role in cell differentiation.

| S-EPMC8883576 | biostudies-literature

LATS1 controls CTCF chromatin occupancy and hormonal response of 3D-grown breast cancer cells

Project description:The cancer epigenome has been studied in cells cultured in two-dimensional (2D) monolayers, but recent studies highlight the impact of the extracellular matrix and the three-dimensional (3D) environment on multiple cellular functions. Here, we report the physical, biochemical, and genomic differences between T47D breast cancer cells cultured in 2D and as 3D spheroids. Cells within 3D spheroids exhibit a rounder nucleus with less accessible, more compacted chromatin, as well as altered expression of ~2,000 genes, the majority of which become repressed. Hi-C analysis reveals that cells in 3D are enriched for regions belonging to the B-compartment, have decreased chromatin-bound CTCF and increased fusion of topologically associating domains (TADs). Upregulation of the Hippo pathway in 3D spheroids results in the activation of the LATS1 kinase, which promotes phosphorylation and displacement of CTCF from DNA, thereby likely causing the observed TAD fusions. 3D cells show higher chromatin binding of progesterone receptor (PR), leading to an increase in the number of hormone-regulated genes. This effect is in part mediated by LATS1 activation, which favors cytoplasmic retention of YAP and CTCF removal.

| S-SCDT-10_1038-S44318-024-00080-X | biostudies-other

CTCF-mediated functional chromatin interactome in pluripotent cells.

Project description:Mammalian genomes are viewed as functional organizations that orchestrate spatial and temporal gene regulation. CTCF, the most characterized insulator-binding protein, has been implicated as a key genome organizer. However, little is known about CTCF-associated higher-order chromatin structures at a global scale. Here we applied chromatin interaction analysis by paired-end tag (ChIA-PET) sequencing to elucidate the CTCF-chromatin interactome in pluripotent cells. From this analysis, we identified 1,480 cis- and 336 trans-interacting loci with high reproducibility and precision. Associating these chromatin interaction loci with their underlying epigenetic states, promoter activities, enhancer binding and nuclear lamina occupancy, we uncovered five distinct chromatin domains that suggest potential new models of CTCF function in chromatin organization and transcriptional control. Specifically, CTCF interactions demarcate chromatin-nuclear membrane attachments and influence proper gene expression through extensive cross-talk between promoters and regulatory elements. This highly complex nuclear organization offers insights toward the unifying principles that govern genome plasticity and function.

| S-EPMC3436933 | biostudies-literature

Time-dependent effect of 1,6-hexanediol on biomolecular condensates and 3D chromatin organization.

Project description:BackgroundBiomolecular condensates have been implicated in multiple cellular processes. However, the global role played by condensates in 3D chromatin organization remains unclear. At present, 1,6-hexanediol (1,6-HD) is the only available tool to globally disrupt condensates, yet the conditions of 1,6-HD vary considerably between studies and may even trigger apoptosis.ResultsIn this study, we first analyzed the effects of different concentrations and treatment durations of 1,6-HD and found that short-term exposure to 1.5% 1,6-HD dissolved biomolecular condensates whereas long-term exposure caused aberrant aggregation without affecting cell viability. Based on this condition, we drew a time-resolved map of 3D chromatin organization and found that short-term treatment with 1.5% 1,6-HD resulted in reduced long-range interactions, strengthened compartmentalization, homogenized A-A interactions, B-to-A compartment switch and TAD reorganization, whereas longer exposure had the opposite effects. Furthermore, the long-range interactions between condensate-component-enriched regions were markedly weakened following 1,6-HD treatment.ConclusionsIn conclusion, our study finds a proper 1,6-HD condition and provides a resource for exploring the role of biomolecular condensates in 3D chromatin organization.

| S-EPMC8369800 | biostudies-literature

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