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Study of three-dimensional structure of chromatin through a 4C-seq experiments in mouse

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

ORGANISM(S): Mus musculus

PROVIDER: GSE197013 | GEO | 2022/04/21

REPOSITORIES: GEO

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Study of three-dimensional structure of chromatin through a 4C-seq experiments in mouse

Project description:Study of three-dimensional structure of chromatin through a 4C-seq experiments in mouse

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Study of three-dimensional structure of chromatin through a 4C-seq experiment in mouse NSC shControl and shJMJD3 upon TGFβ treatment [Chst8]

Project description:In this study we analyzed how multiple enhancers arrange in the 3D-space to control the activation of a specific promoter. Specifically, we did a 4C-seq experiment on a ~374 Kb locus where enhancers abound, which revealed that the TGFβ pathway drives the establishment of contacts between cis-regulatory elements that facilitates the assembly of an enhancer-cluster and precise gene activation. We discovered that the TGFβ pathway coactivator JMJD3 is essential to maintain these 3D-structures, as when it is depleted the contacts are lost but they are restablished when re-expressing the protein. To do that, JMJD3 requires a proline-rich intrinsically disordered region, which is essential for proper gene activation due to its involvement in the formation of phase-separated biomolecular condensates. Overall, we uncover novel functions for the ubiquitous coactivator JMJD3, and we shed light on the relationships between the 3D-conformation of the chromatin, and their role in regulating the TGFβ-driven response during mammalian neurogenesis.

2022-04-21 | GSE197010 | GEO

Study of three-dimensional structure of chromatin through a 4C-seq experiment in mouse NSC shControl and shJMJD3 upon TGFβ treatment [Ldlrad4]

Project description:In this study we analyzed how multiple enhancers arrange in the 3D-space to control the activation of a specific promoter. Specifically, we did three 4C-seq experiments on different genomic loci where enhancers abound - Chst8, Ldlrad4 and Aopep, which revealed that the TGFβ pathway drives the establishment of contacts between cis-regulatory elements. Furthermore, we discovered that the TGFβ pathway coactivator JMJD3 is essential to maintain these 3D-structures. Specifically, in the Chst8 locus JMJD3 requires a proline-rich intrinsically disordered region to properly induce these loops, and hence gene activation, due to its involvement in the formation of phase-separated biomolecular condensates. Overall, we uncover novel functions for the ubiquitous coactivator JMJD3, and we shed light on the relationships between the 3D-conformation of the chromatin, and their role in regulating the TGFβ-driven response during mammalian neurogenesis.

2022-04-21 | GSE197012 | GEO

Study of three-dimensional structure of chromatin through a 4C-seq experiment in mouse NSC shControl and shJMJD3 upon TGFβ treatment [Aopep]

2022-04-21 | GSE197011 | GEO

Generation of dynamic three-dimensional genome structure through phase separation of chromatin.

Project description:Three-dimensional genome structure and dynamics play critical roles in regulating DNA functions. Flexible chromatin structure and movements suggested that the genome is dynamically phase separated to form A (active) and B (inactive) compartments in interphase nuclei. Here, we examine this hypothesis by developing a polymer model of the whole genome of human cells and assessing the impact of phase separation on genome structure. Upon entry to the G1 phase, the simulated genome expanded according to heterogeneous repulsion among chromatin chains, which moved chromatin heterogeneously, inducing phase separation of chromatin. This repulsion-driven phase separation quantitatively reproduces the experimentally observed chromatin domains, A/B compartments, lamina-associated domains, and nucleolus-associated domains, consistently explaining nuclei of different human cells and predicting their dynamic fluctuations. We propose that phase separation induced by heterogeneous repulsive interactions among chromatin chains largely determines dynamic genome organization.

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The three-dimensional structure of chromatin condensed by PRC1 is porous and accessible

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-03-07 | GSE220140 | GEO

A phase separation mechanism underlies development of cancer and aberrant organization of three-dimensional chromatin structure

Project description:This SuperSeries is composed of the SubSeries listed below.

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Three-dimensional chromatin landscapes in MLLr AML

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-02-20 | GSE244472 | GEO

Integrative characterization of G-Quadruplexes in the three-dimensional chromatin structure.

Project description:DNA molecules are highly compacted in the eukaryotic nucleus where distal regulatory elements reach their targets through three-dimensional chromosomal interactions. G-quadruplexes, stable four-stranded non-canonical DNA structures, can change local chromatin organization through the exclusion of nucleosomes. However, the relationship between G-quadruplexes and higher-order genome organization remains unknown. Here, we found that G-quadruplexes are significantly enriched at boundaries of topological associated domains (TADs). Architectural protein occupancy, which plays critical roles in the formation of TADs, was highly correlated with the content of G-quadruplexes at TAD boundaries. Moreover, adjacent boundaries containing G-quadruplexes frequently interacted with each other because of the high enrichment of architectural protein binding sites. Similar to CCCTC-binding factor (CTCF) binding sites, G-quadruplexes also showed strong insulation ability in the separation of adjacent regions. Additionally, the insulation ability of CTCF binding sites and TAD boundaries was significantly reinforced by G-quadruplexes. Furthermore, G-quadruplex motifs on different strands were associated with the orientation of CTCF binding sites. These findings suggest a potential role for G-quadruplexes in loop extrusion. The enrichment of transcription factor binding sites (TFBSs) around regulatory elements containing G-quadruplexes led to frequent interactions between regulatory elements containing G-quadruplexes. Intriguingly, more than 99% of G-quadruplexes overlapped with TFBSs. The binding sites of CTCF and cohesin proteins were preferentially located surrounding G-quadruplexes. Accordingly, we proposed a new mechanism of long-distance gene regulation in which G-quadruplexes are involved in distal interactions between enhancers and promoters.

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Enhancers as regulators of antigen receptor loci three-dimensional chromatin structure.

Project description:Enhancers are defined as regulatory elements that control transcription in a cell-type and developmental stage-specific manner. They achieve this by physically interacting with their cognate gene promoters. Significantly, these interactions can occur through long genomic distances since enhancers may not be near their cognate promoters. The optimal coordination of enhancer-regulated transcription is essential for the function and identity of the cell. Although great efforts to fully understand the principles of this type of regulation are ongoing, other potential functions of the long-range chromatin interactions (LRCIs) involving enhancers are largely unexplored. We recently uncovered a new role for enhancer elements in determining the three-dimensional (3D) structure of the immunoglobulin kappa (Igκ) light chain receptor locus suggesting a structural function for these DNA elements. This enhancer-mediated locus configuration shapes the resulting Igκ repertoire. We also propose a role for enhancers as critical components of sub-topologically associating domain (subTAD) formation and nuclear spatial localization.

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