PXD070894

PXD070894 is an original dataset announced via ProteomeXchange.

Title	CTCF couples long-range loop extrusion and diffusion to mediate a diverse Igk repertoire
Description	Dynamic genome folding is important for V(D)J recombination at the immunoglobulin kappa (Igk) locus, which recombines Jk and Vk gene segments across a 3.2 Mb region in both deletional and inversional orientations. Chromatin loop extrusion and diffusion are considered two key mechanisms underlying Igk folding, but how they coordinate remains unclear. Here we show that CTCF is a key regulator coupling loop extrusion and diffusion during Igk V-J rearrangement, promoting recombination in both orientations across long genomic distances. Mechanistically, the CTCF N-terminus promotes long-range loop extrusion that facilitates distal Vk usage by stabilizing cohesin against WAPL release, and also forms loop barriers enabling chromatin diffusion for inversional Vk joining. In CTCF N-terminal-deficient B cells, defects in inversional Vk joining are not restored by WAPL depletion but are instead largely rescued by a dCas9-blockade targeted to the Vk-Jk intergenic region, mimicking the CTCF barrier. Our findings thus highlight how CTCF coordinates distinct genome-folding mechanisms through its dual roles in cohesin stabilization and extrusion barrier formation to ensure the generation of a diverse Igk repertoire.
HostingRepository	PRIDE
AnnounceDate	2025-11-18
AnnouncementXML	Submission_2025-11-18_12:20:40.504.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jorge Colon Rosado
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-18 08:51:37	ID requested
⏵ 1	2025-11-18 12:20:41	announced

Dataset with its publication pending

submitter keyword: Molecular biology, Biological sciences, VDJ recombination,Biological sciences, Immunology, Chromatin, Chromatin structure, Adaptive immunity

Liangliang Sun
contact affiliation	Department of Chemistry Michigan State University
contact email	lsun@chemistry.msu.edu
lab head
Jorge Colon Rosado
contact affiliation	Michigan State University
contact email	colonros@msu.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/11/PXD070894

PRIDE project URI

• PRIDE
  1. PXD070894
     1. Label: PRIDE project
     2. Name: CTCF couples long-range loop extrusion and diffusion to mediate a diverse Igk repertoire