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A de novo transcription-dependent TAD boundary underpins critical multiway interactions during antibody class switch recombination [Tri-C]

ABSTRACT: A de novo transcription-dependent TAD boundary underpins critical multiway interactions during antibody class switch recombination [Tri-C]

PROVIDER: PRJNA814070 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18274700_1.fastq.gz	Fastqsanger.gz
	SRR18274700_2.fastq.gz	Fastqsanger.gz
	SRR18274701_1.fastq.gz	Fastqsanger.gz
	SRR18274701_2.fastq.gz	Fastqsanger.gz
	SRR18274702_1.fastq.gz	Fastqsanger.gz

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A de novo transcription-dependent TAD boundary underpins critical multiway interactions during antibody class switch recombination

Project description:A de novo transcription-dependent TAD boundary underpins critical multiway interactions during antibody class switch recombination

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A de novo transcription-dependent TAD boundary underpins critical multiway interactions during antibody class switch recombination [ChIP-Seq]

Project description:A de novo transcription-dependent TAD boundary underpins critical multiway interactions during antibody class switch recombination [ChIP-Seq]

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A de novo transcription-dependent TAD boundary underpins critical multiway interactions during antibody class switch recombination [PRO-seq]

Project description:A de novo transcription-dependent TAD boundary underpins critical multiway interactions during antibody class switch recombination [PRO-seq]

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A de novo transcription-dependent TAD boundary underpins critical multiway interactions during antibody class switch recombination [Micro-C]

Project description:A de novo transcription-dependent TAD boundary underpins critical multiway interactions during antibody class switch recombination [Micro-C]

| PRJNA814068 | ENA

A de novo transcription-dependent TAD boundary underpins critical multiway interactions during antibody class switch recombination [Tri-C]

Project description:Antibody class switch recombination (CSR) requires the ligation of DNA breaks in transcribed and juxtaposed donor and acceptor switch (S) sequences (S-S synapsis) spaced 50-200 kb apart within the immunoglobulin heavy chain locus (Igh). CSR is believed to occur via the association of active S regions with the 3’ regulatory region (3’RR) super-enhancer thereby coupling transcription with S-S synapsis. Here, we map the multi-way interactome underlying CSR using Tri-C. Surprisingly, S-S synapsis is strongly associated with the 3` CTCF binding element (3`CBE), but not the 3’RR, a finding also confirmed by Micro-C measurements. Instead, the 3’RR forms a self-interacting domain independently engaging with Igh genes. Additionally, transcription at acceptor S regions creates a topological barrier that insulates S-S synapsis from loop extrusion complexes. Thus, Igh gene activation and S-S synapsis occur via distinct topological states created by the interaction between transcription and the loop extrusion machinery.

2023-01-20 | GSE198179 | GEO

TAD Evolutionary and functional characterization reveals diversity in mammalian TAD boundary properties and function

Project description:Topological associating domains (TADs) are self-interacting genomic units crucial for shaping gene regulation patterns. Despite their importance, the extent of their evolutionary conservation and its functional implications remain largely unknown. In this study, we generate Hi-C and ChIP-seq data and compare TAD organization across four primate and four rodent species, and characterize the genetic and epigenetic properties of TAD boundaries in correspondence to their evolutionary conservation. We find 14% of all human TAD boundaries to be shared among all eight species (ultraconserved), while 15% are human-specific. Ultraconserved TAD boundaries have stronger insulation strength, CTCF binding, and enrichment of older retrotransposons, compared to species-specific boundaries. CRISPR-Cas9 knockouts of two ultraconserved boundaries in mouse models leads to tissue-specific gene expression changes and morphological phenotypes. Deletion of a human-specific boundary near the autism-related AUTS2 gene results in upregulation of this gene in neurons. Overall, our study provides pertinent TAD boundary evolutionary conservation annotations, and showcase the functional importance of TAD evolution.

2023-10-20 | GSE197926 | GEO

A de novo transcription-dependent TAD boundary underpins critical multiway interactions during antibody class switch recombination [Micro-C]

2023-01-20 | GSE198181 | GEO

A de novo transcription-dependent TAD boundary underpins critical multiway interactions during antibody class switch recombination [PRO-seq]

2023-01-20 | GSE198180 | GEO

A de novo transcription-dependent TAD boundary underpins critical multiway interactions during antibody class switch recombination [ChIP-Seq]

2023-01-20 | GSE198176 | GEO

A TAD boundary is preserved upon deletion of the CTCF-rich Firre locus

Project description:ABSTRACT The binding of the transcriptional regulator CTCF to the genome has been implicated in the formation of topologically associated domains (TADs). However, the general mechanisms of folding the genome into TADs are not fully understood. Here, we tested the effects of deleting a CTCF-rich locus on TAD boundary formation. Using genome-wide chromosome conformation capture (Hi-C), we focus on one TAD boundary on chromosome X harboring ~15 CTCF binding sites, and located at the long non-coding RNA (lncRNA) locus Firre. Specifically, this TAD boundary is invariant across evolution, tissues, and temporal dynamics of X-chromosome inactivation. We demonstrate that neither the deletion of this locus, nor the ectopic insertion of Firre cDNA or its ectopic expression are sufficient to alter TADs in a sex-, or allele-specific manner. In contrast, Firre’s deletion disrupts the chromatin super-loop formation of the inactive X-chromosome. Collectively, our findings suggest that apart from CTCF binding, additional mechanisms may play roles in establishing TAD boundary formation. This SuperSeries is composed of the SubSeries listed below.

2018-02-12 | GSE98632 | GEO

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