Organization principles of dynamic three- dimensional genome architecture associated with centromere clustering states

• 成果类型: Article
• 署名作者: Polisetty, Satya Dev; Dutta, Shuvadip; Vadnala, Rakesh Netha; Notani, Dimple; Padinhateeri, Ranjith; Sanyal, Kaustuv
• 署名单位: Department of Science & Technology (India); Jawaharlal Nehru Center for Advanced Scientific Research (JNCASR); Indian Institute of Technology System (IIT System); Indian Institute of Technology (IIT) - Bombay; Tata Institute of Fundamental Research (TIFR); National Centre for Biological Sciences (NCBS); Indian Institute of Technology System (IIT System); Indian Institute of Technology (IIT) - Bombay; Indian Institute of Technology System (IIT System); Indian Institute of Technology (IIT) - Bombay; Indian Institute of Technology System (IIT System); Indian Institute of Technology (IIT) - Bombay; Department of Science & Technology (India); Bose Institute
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2520310122
• 发表日期: 2025-12-16
• 页码: e2520310122
• 关键词: 3d genome; Rabl configuration; centromere clustering; DNA replication timing; dna-replication; CHROMATIN INTERACTIONS; binding protein; fission yeast; heterochromatin; chromosomes; domains; determinant; origins

摘要

Fungal centromeres are clustered near microtubule organizing centers to help adopt the Rabl chromosomal organization. The role of centromere clustering in driving large-scale changes in structural and functional chromatin assembly remains unclear. Here, using Hi-C and superresolution microscopy, we show that cell cycle-dependent centromere declustering and clustering states in Cryptococcus neoformans drive global changes in the 3D genome architecture. Centromeres and telomeres are scattered around the nuclear periphery at interphaseG1, and this arrangement constrains the interarm interactions within a chromosome, providing a unique interphaseG1 chromosome organization. Moreover, centromeres and telomeres are organized as separate compartments, segregating them from active euchromatic regions. Polymer modeling reveals that the transition from the unclustered to clustered centromere state during the cell cycle involves changes from a globular to an elongated chromosome architecture. Strikingly, while clustered centromeric regions replicate early in most yeasts, C. neoformans centromeres replicate late in S-phase, hinting at a possible link between centromere clustering dynamics and CENDNA replication timing. Overall, our study uncovers several unique organizational principles governing the dynamic genome architecture in an evolutionarily diverged basidiomycete yeast.