Condensin DC loads and spreads from recruitment sites to create loop-anchored TADs in C. elegans

Jun Kim, David S. Jimenez, Bhavana Ragipani, Bo Zhang, Lena A. Street, Maxwell Kramer, Sarah E. Albritton, Lara H. Winterkorn, Ana K. Morao, Sevinc Ercan

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Condensins are molecular motors that compact DNA via linear translocation. In Caenorhabditis elegans, the X-chromosome harbors a specialized condensin that participates in dosage compensation (DC). Condensin DC is recruited to and spreads from a small number of recruitment elements on the X-chromosome (rex) and is required for the formation of topologically associating domains (TADs). We take advantage of autosomes that are largely devoid of condensin DC and TADs to address how rex sites and condensin DC give rise to the formation of TADs. When an autosome and X-chromosome are physically fused, despite the spreading of condensin DC into the autosome, no TAD was created. Insertion of a strong rex on the X-chromosome results in the TAD boundary formation regardless of sequence orientation. When the same rex is inserted on an autosome, despite condensin DC recruitment, there was no spreading or features of a TAD. On the other hand, when a ‘super rex’ composed of six rex sites or three separate rex sites are inserted on an autosome, recruitment and spreading of condensin DC led to the formation of TADs. Therefore, recruitment to and spreading from rex sites are necessary and sufficient for recapitulating loop-anchored TADs observed on the X-chromosome. Together our data suggest a model in which rex sites are both loading sites and bidirectional barriers for condensin DC, a one-sided loop-extruder with movable inactive anchor.

Original languageEnglish (US)
Article numbere68745
JournaleLife
Volume11
DOIs
StatePublished - 2022

Bibliographical note

Funding Information:
SE and research in this manuscript were supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number R35 GM130311. DJ, JK, and MK were supported in part by NIGMS Predoctoral Fellowship T32HD007520. We thank Dr. Noelle L’etoile, who generously supported Bo Zhang’s postdoctoral work that included dCas9 targeting, with grants NIBIB R33 EB019784 and NIDCD R01 DC005991. We thank Jordan Ward and Baohui Chen for plasmids. We thank Gencore at the NYU Center for Genomics and Systems Biology. We also thank Shaun Mahony, Lila Rieber, Pedro Rocha, Ramya Raviram and Jane Skok who helped with experimental trials prior to adopting Hi-C, and Arima genomics for technical support.

Publisher Copyright:
© Kim, Jimenez et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

Fingerprint

Dive into the research topics of 'Condensin DC loads and spreads from recruitment sites to create loop-anchored TADs in C. elegans'. Together they form a unique fingerprint.

Cite this