TAD cliques shape the 4-dimensional genome during dual lineage terminal differentiation
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE109924 | GEO | 2019/02/23
REPOSITORIES: GEO
Similar Datasets
Project description:TAD cliques shape the 4-dimensional genome during dual lineage terminal differentiation
| PRJNA432349 | ENA
Project description:BackgroundMechanisms underlying genome 3D organization and domain formation in the mammalian nucleus are not completely understood. Multiple processes such as transcriptional compartmentalization, DNA loop extrusion and interactions with the nuclear lamina dynamically act on chromatin at multiple levels. Here, we explore long-range interaction patterns between topologically associated domains (TADs) in several cell types.ResultsWe find that TAD long-range interactions are connected to many key features of chromatin organization, including open and closed compartments, compaction and loop extrusion processes. Domains that form large TAD cliques tend to be repressive across cell types, when comparing gene expression, LINE/SINE repeat content and chromatin subcompartments. Further, TADs in large cliques are larger in genomic size, less dense and depleted of convergent CTCF motifs, in contrast to smaller and denser TADs formed by a loop extrusion process.ConclusionsOur results shed light on the organizational principles that govern repressive and active domains in the human genome.
| S-EPMC8254932 | biostudies-literature
Project description:The ability to recapitulate muscle differentiation in vitro has proven invaluable to investigate mechanisms of myogenesis, muscle cell function and muscle diseases. However, obtaining myoblasts from patients with neuromuscular diseases poses ethical and procedural challenges which limit investigations of molecular mechanisms of muscle pathophysiology. Alternative myogenic models have been developed, such as the derivation of myogenic cells from skin fibroblasts through activation of an endogenous myogenic program triggered by exogenous expression of murine Myod. In the context of this ChIP-seq dataset, we compared the transcriptome and lamina-associated domains (LADs) as genome organizers in myo-converted human fibroblasts and in isogenic myotubes differentiated from myoblasts. We show that myogenic induction of fibroblasts elicits genome-wide transcriptomic changes indicative of myogenic commitment and differentiation. Yet, myotubes are further along myogenic commitment than myo-converted fibroblasts under the conditions tested. LADs with typical LAD properties (low gene density, containing mostly repressed genes, and H3K9me3-rich) are shared between the two cell types, but each cell type also displays nearly 700 unique LADs. Strikingly, myotube-specific LADs are smaller, more gene-rich and less heterochromatic than shared LADs or LADs unique to myo-converted fibroblasts. Thus, myo-converted fibroblasts and myotubes retain some cell type specificity of genome organization at this level. Although these myogenic cell types are not identical, our results favor a view of myo-converted fibroblasts as a robust and practical model to investigate cellular and genomic properties of cells from patients with muscle pathologies.
2023-08-21 | GSE236115 | GEO
Project description:Background: The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized three-dimensional (3D) chromatin architecture and dynamics remains poorly understood. Results: Here by combining imaging and sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to chromatin redistribution and decompaction. Consequently, lamina-associated domains (LADs) are detached from the nuclear periphery. The inter-chromosomal interactions and overlap between chromosome territories are increased. Moreover, Hi-C data revealed that lamin B1 is required for the integrity and segregation of chromatin compartments but not for the topologically associating domains (TADs). Using live cell single molecule tracking, we further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nucleoplasm. Conclusions: Taken together, our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance, genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics, supporting its crucial role in chromatin higher-order structure and chromatin dynamics.
2020-11-08 | GSE124409 | GEO
Project description:The mammalian genome is intricately folded in a three-dimensional topology believed to be important for the orchestration of gene expression regulating development, differentiation and tissue homeostasis. Important features of spatial genome conformation in the nucleus are promoter-enhancer contacts regulating gene expression within topologically-associated domains (TADs), short- and long-range interactions between TADs and associations of chromatin with nucleoli and nuclear speckles. In addition, anchoring of chromosomes to the nuclear lamina via lamina-associated domains (LADs) at the nuclear periphery is a key regulator of the radial distribution of chromatin. To what extent TADs and LADs act in concert as genomic organizers to shape the three-dimensional topology of chromatin has long remained unknown. A new study addressing this key question provides evidence of (i) preferred long-range associations between TADs forming TAD "cliques" which organize large heterochromatin domains, and (ii) stabilization of TAD cliques by LADs at the nuclear periphery after induction of terminal differentiation. Here, we review these findings, address the issue of whether TAD cliques exist in single cells and discuss the extent of cell-to-cell heterogeneity in higher-order chromatin conformation. The recent observations provide a first appreciation of changes in 4-dimensional higher-order genome topologies during differentiation.
| S-EPMC6593077 | biostudies-literature
Project description:We develop Split-Pool Recognition of Interactions by Tag Extension (SPRITE), which enables genome-wide detection of higher-order interactions that occur simultaneously within the nucleus in a proximity-ligation independent manner. We generated SPRITE maps in two mammalian cell types – mouse embryonic stem cells (mES) and human lymphoblastoid cells (GM12878). We generated ~1.5 billion sequencing reads from each sample and recapitulate known genome structures identified by Hi-C, including chromosome territories, compartments, topologically associated domains, and loop structures, and identify that many of these occur within higher-order structures in the nucleus. Because SPRITE does not rely on proximity-ligation, we find that SPRITE identifies interactions that occur across larger spatial distances than can be observed by Hi-C. These long-range interactions include two major hubs of inter-chromosomal interactions. We extended SPRITE to enable simultaneous measurements of RNA and DNA interactions and observe ribosomal RNA interactions across specific regions on the genome that correspond to DNA organization around the nucleolus. We show that gene-dense regions that are highly transcribed by PolII organize around nuclear speckles and gene poor, and therefore transcriptionally inactive, regions that are centromere-proximal organize around the nucleolus. In addition to the regions that directly associate around these nuclear bodies, we find that a substantial fraction of the genome exhibits preferential spatial positioning in the nucleus relative to each of these nuclear bodies and that the spatial preferences identified by SPRITE are highly correlated with 3D distances measured by microscopy.
2018-06-07 | GSE114242 | GEO
Project description:A large fraction of the mammalian genome is organized into inactive chromosomal domains associated with the nuclear lamina. Using genomic repositioning assays we show that Lamina associated domains (LADs), spanning the developmentally regulated IgH and Cyp3a loci, contain transportable DNA regions that associate chromatin with the nuclear lamina and repress gene activity in fibroblasts. We characterized DNA regions within LADs that are functionally capable of positioning chromatin domains at the inner nuclear membrane (INM) lamina. We mapped and characterized the IgH and other LADs in murine fibroblasts. We show that these murine LADs have a unique chromatin structure with discrete boundaries. We demonstrate DNA regions within LADs that are capable of directing the association of chromatin domains with the INM-lamina as well as the silencing of a co-integrated reporter gene.
2012-02-24 | E-GEOD-36048 | biostudies-arrayexpress
Project description:The nuclear lamina (NL) interacts with hundreds of large genomic regions termed lamina-associated domains (LADs). The dynamics of these interactions and the relation to epigenetic modifications are poorly understood. We visualized the fate of LADs in single cells using a novel 'molecular contact memory' approach. In each interphase nucleus, only ~30% of LADs are positioned at the periphery; these LADs are in intermittent molecular contact with the NL but remain constrained to the periphery. Upon mitosis, LAD positioning is not detectably inherited but instead is stochastically reshuffled. Contact of individual LADs with the NL correlates with their degree of H3K9 dimethylation in single cells, and inactivation of the H3K9 methyltransferase G9a reduces the NL contact frequencies. These results indicate that nuclear positioning and histone modification of LADs are both stochastic yet linked in single cells. Collectively, these results highlight principles of the dynamic spatial architecture of chromosomes. LaminB1-chromatin interactions were assayed in human HT1080 cells by induction of Dam_LMNB1 expression in a stable cell line with shield1.
2013-01-31 | E-GEOD-40094 | biostudies-arrayexpress
Project description:The nuclear lamina (NL) interacts with hundreds of large genomic regions termed lamina-associated domains (LADs). The dynamics of these interactions and the relation to epigenetic modifications are poorly understood. We visualized the fate of LADs in single cells using a novel 'molecular contact memory' approach. In each interphase nucleus, only ~30% of LADs are positioned at the periphery; these LADs are in intermittent molecular contact with the NL but remain constrained to the periphery. Upon mitosis, LAD positioning is not detectably inherited but instead is stochastically reshuffled. Contact of individual LADs with the NL correlates with their degree of H3K9 dimethylation in single cells, and inactivation of the H3K9 methyltransferase G9a reduces the NL contact frequencies. These results indicate that nuclear positioning and histone modification of LADs are both stochastic yet linked in single cells. Collectively, these results highlight principles of the dynamic spatial architecture of chromosomes. 12 RNA-seq experiments for 6 samples, each with a biological replicate: m6ATracer-VP16+/DamLaminB1+ m6ATracer-VP16+/DamLaminB1- m6ATracer-VP16-/DamLaminB1- m6ATracer-GFP+/DamLaminB1+ m6ATracer-GFP+/DamLaminB1- m6ATracer-GFP-/DamLaminB1-
2013-01-31 | E-GEOD-40111 | biostudies-arrayexpress
Project description:The nuclear lamina provides a repressive chromatin environment at the nuclear periphery. However, whereas most genes in lamina-associated domains (LADs) are repressed, approximately ten percent reside in local euchromatic contexts and are expressed. How these genes are regulated and whether they are able to contact regulatory elements in LADs or outside LADs remains unclear. Here, we integrate transcriptomic, chromatin states, microscopy and publicly available enhancer-capture Hi-C data to show that expressed genes in LADs are able to connect to enhancers in LADs and inter-LADs. Our data favor a model where the spatial topology of chromatin at the nuclear lamina is compatible with transcriptional regulation in this dynamic nuclear compartment.
2023-01-01 | GSE221288 | GEO