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

• Published in: eLife Vol. 11
• Main Authors: Kim, Jun, Jimenez, David S, Ragipani, Bhavana, Zhang, Bo, Street, Lena A, Kramer, Maxwell, Albritton, Sarah E, Winterkorn, Lara H, Morao, Ana K, Ercan, Sevinc
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 04.11.2022; eLife Sciences Publications Ltd; eLife Sciences Publication; eLife Sciences Publications, Ltd
• Subjects: 3D genome organization; Animals; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Cell cycle; Chromosomes; Chromosomes and Gene Expression; Condensin; Dosage compensation; Dosage compensation (Genetics); Dosage Compensation, Genetic; Embryos; Gene expression; Gene Expression Regulation; Genetic aspects; Genetic research; Genetics and Genomics; Genomes; Hi-C; Life Sciences; loop extrusion; Mammals; Molecular motors (Biochemistry); Physiological aspects; Recruitment; Ribosomal DNA; Spreading; TADs; X Chromosome - genetics; X chromosomes; X-chromosome; Yeast; United States; C. elegans; condensin; genetics; Hi-C; 3D genome organization; chromosomes; X-chromosome; genomics; TADs; gene expression; loop extrusion
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.68745

Condensins are molecular motors that compact DNA via linear translocation. In , 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 ecruitment lements on the -chromosome ( ) 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 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 on the X-chromosome results in the TAD boundary formation regardless of sequence orientation. When the same is inserted on an autosome, despite condensin DC recruitment, there was no spreading or features of a TAD. On the other hand, when a ' ' composed of six sites or three separate sites are inserted on an autosome, recruitment and spreading of condensin DC led to the formation of TADs. Therefore, recruitment to and spreading from sites are necessary and sufficient for recapitulating loop-anchored TADs observed on the X-chromosome. Together our data suggest a model in which sites are both loading sites and bidirectional barriers for condensin DC, a one-sided loop-extruder with movable inactive anchor.