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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 [Aopep]

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 | GSE197011 | GEO

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.

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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 [Ldlrad4]

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

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

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

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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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