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  3. Imbalanced chromatin distribution in cellular senescence specifies paraspeckle dynamics

Imbalanced chromatin distribution in cellular senescence specifies paraspeckle dynamics

  • Genome Biol. 2025 Sep 2;26(1):264. doi: 10.1186/s13059-025-03757-6.
Joonwoo Lee 1,  Jinmi Choi 2,  Jeongeun Park 3,  Seonduk Lee 1,  Eun-Jung Cho 2,  Youngdae Gwon 4 5 6
Affiliations

Affiliations

  • 1 Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, 16419, Republic of Korea.
  • 2 Sungkyunkwan University School of Pharmacy, Suwon, 16419, Republic of Korea.
  • 3 Department of MetaBioHealth, Sungkyunkwan University Institute for Convergence, Suwon, 16419, Republic of Korea.
  • 4 Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, 16419, Republic of Korea. ygwon@skku.edu.
  • 5 Department of MetaBioHealth, Sungkyunkwan University Institute for Convergence, Suwon, 16419, Republic of Korea. ygwon@skku.edu.
  • 6 KIST-SKKU Brain Research Center, Sungkyunkwan University Institute for Convergence, Suwon, 16419, Republic of Korea. ygwon@skku.edu.
PMID: 40898359 DOI: 10.1186/s13059-025-03757-6
Abstract

Cellular senescence is accompanied by extensive genomic reorganization, such as senescence-associated heterochromatin foci and expanded interchromatin compartments, to ultimately affect gene expression. Here, we demonstrate that chromatin structural changes in senescent cells drive significant alterations in the phase behavior and motility of paraspeckles, a type of interchromatin compartment condensate. We observe increased numbers, size, and elongation of paraspeckles harboring NONO and NEAT1_2, driven by elevated levels of those components, consistent with the micellization model of longitudinal growth rather than condensate coalescence. Enhanced paraspeckle motility is associated with HP1α-mediated heterochromatin condensation and interchromatin expansion found in cellular senescence.

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