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Loop Extrusion Mediates Physiological Locus Contraction for V(D)J Recombination (ChIP-Seq)

ABSTRACT: Loop Extrusion Mediates Physiological Locus Contraction for V(D)J Recombination (ChIP-Seq)

PROVIDER: PRJNA637630 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11936600_1.fastq.gz	Fastqsanger.gz
	SRR11936600_2.fastq.gz	Fastqsanger.gz
	SRR11936601_1.fastq.gz	Fastqsanger.gz
	SRR11936601_2.fastq.gz	Fastqsanger.gz
	SRR11936602_1.fastq.gz	Fastqsanger.gz

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Loop Extrusion Mediates Physiological Locus Contraction for V(D)J Recombination

Project description:Loop Extrusion Mediates Physiological Locus Contraction for V(D)J Recombination

| PRJNA637627 | ENA

Loop Extrusion Mediates Physiological Locus Contraction for V(D)J Recombination (3C-HTGTS)

Project description:Immunoglobulin heavy chain locus (Igh) VH, D, and JH gene segments are developmentally assembled into V(D)J exons. RAG endonuclease initiates V(D)J recombination by binding a JH-recombination signal sequence (RSS) within a chromatin-based recombination center (RC) and then, in an orientation-dependent process, scans upstream D-containing chromatin presented by cohesin-mediated loop extrusion for convergent D-RSSs to initiate DJH-RC formation. In primary pro-B cells, 100s of upstream VH-associated RSSs, embedded in convergent orientation to the DJH-RC-RSS, gain proximity to the DJH-RC for VH-to-DJH joining via a mechanistically-undefined VH-locus contraction process. Here, we report that a 2.4 mega-base VH locus inversion in primary pro-B cells nearly abrogates rearrangements of normally convergent VH-RSSs and cryptic RSSs, even though locus contraction per se is maintained. Moreover, this inversion activated rearrangement of both cryptic VH-locus RSSs normally in the opposite orientation and, unexpectedly, of normally-oriented cryptic RSSs within multiple, sequential upstream convergent-CBE domains. Primary pro-B cells had significantly reduced transcription of Wapl, a cohesin-unloading factor, versus levels in v-Abl pro-B lines that lack marked locus contraction or distal VH rearrangements. Correspondingly, Wapl depletion in v-Abl lines activated VH-locus contraction and orientation-specific RAG-scanning across the VH-locus. Our findings indicate that locus contraction and physiological VH-to-DJH joining both are regulated via circumvention of CBE scanning impediments.

2020-11-08 | GSE151909 | GEO

Loop Extrusion Mediates Physiological Locus Contraction for V(D)J Recombination (ChIP-Seq)

2020-11-08 | GSE151908 | GEO

Loop Extrusion Mediates Physiological Locus Contraction for V(D)J Recombination (GRO-Seq)

2020-11-08 | GSE151907 | GEO

Loop Extrusion Mediates Physiological Locus Contraction for V(D)J Recombination (LAM-HTGTS)

2020-11-08 | GSE151906 | GEO

Loop Extrusion Mediates Physiological Locus Contraction for V(D)J Recombination (3C-HTGTS)

Project description:Loop Extrusion Mediates Physiological Locus Contraction for V(D)J Recombination (3C-HTGTS)

| PRJNA637631 | ENA

Loop Extrusion Mediates Physiological Locus Contraction for V(D)J Recombination (GRO-Seq)

Project description:Loop Extrusion Mediates Physiological Locus Contraction for V(D)J Recombination (GRO-Seq)

| PRJNA637624 | ENA

Loop Extrusion Mediates Physiological Locus Contraction for V(D)J Recombination (LAM-HTGTS)

Project description:Loop Extrusion Mediates Physiological Locus Contraction for V(D)J Recombination (LAM-HTGTS)

| PRJNA637625 | ENA

Wapl repression by Pax5 promotes loop extrusion and V gene recombination at the Igh locus

Project description:The generation of a diverse antibody repertoire is essential for humoral immunity and requires the participation of all V genes in V(D)J recombination, which depends on the Pax5-regulated contraction of the 2.8-Mb long immunoglobulin heavy-chain (Igh) locus. How Pax5 controls Igh contraction in pro-B cells is, however, not known. Here, we demonstrate that locus contraction is caused by cohesin-mediated chromatin loop extrusion across the entire Igh locus. Notably, expression of the cohesin-release factor Wapl is repressed by Pax5 specifically in pro-B and pre-B cells, which facilitates extended loop extrusion by increasing the residence time of cohesin on chromatin. Pax5 mediates the transcriptional repression of Wapl through a single Pax5-binding site by recruiting the Polycomb repressive complex 2 to induce bivalent chromatin at the Wapl promoter. Reduced Wapl expression causes global alterations of the three-dimensional chromatin architecture, indicating that the potential to recombine all V genes entails structural changes of the entire genome in pro-B cells.

2020-07-01 | GSE140975 | GEO

Loop Extrusion Mediates Physiological Locus Contraction for V(D)J Recombination

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

2020-11-07 | GSE151910 | GEO