Chromatin decompaction by the nucleosomal binding protein HMGN5 impairs nuclear sturdiness

Takashi Furusawa, Mark Rochman, Leila Taher, Emilios K Dimitriadis, Kunio Nagashima, Stasia Anderson, Michael Bustin

Research output: Contribution to journalArticleResearchpeer-review

Abstract

In most metazoan nuclei, heterochromatin is located at the nuclear periphery in contact with the nuclear lamina, which provides mechanical stability to the nucleus. We show that in cultured cells, chromatin decompaction by the nucleosome binding protein HMGN5 decreases the sturdiness, elasticity and rigidity of the nucleus. Mice overexpressing HMGN5, either globally or only in the heart, are normal at birth but develop hypertrophic heart with large cardiomyoctyes, deformed nuclei and disrupted lamina and die of cardiac malfunction. Chromatin decompaction is seen in cardiomyocytes of newborn mice but misshaped nuclei with disrupted lamina are seen only in adult cardiomyocytes, suggesting that loss of heterochromatin diminishes the ability of the nucleus to withstand the mechanical forces of the contracting heart. Thus, heterochromatin enhances the ability of the nuclear lamina to maintain the sturdiness and shape of the eukaryotic nucleus; a structural role for chromatin that is distinct from its genetic functions.

Original languageEnglish
Pages (from-to)6138
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 22 Jan 2015

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Keywords

  • Age Factors
  • Animals
  • Animals, Newborn
  • Biomechanical Phenomena
  • Cardiomyopathy, Dilated/genetics
  • Cell Nucleus/metabolism
  • Cell Size
  • Elasticity
  • Fibroblasts/cytology
  • Gene Expression Regulation
  • HMGN Proteins/genetics
  • Hardness
  • Heterochromatin/chemistry
  • Histones/genetics
  • Integrases/genetics
  • Lamin Type B/genetics
  • Mice
  • Mice, Transgenic
  • Myocardium/metabolism
  • Myocytes, Cardiac/metabolism
  • NIH 3T3 Cells
  • Nuclear Lamina/metabolism
  • Primary Cell Culture

Cite this

Furusawa, T., Rochman, M., Taher, L., Dimitriadis, E. K., Nagashima, K., Anderson, S., & Bustin, M. (2015). Chromatin decompaction by the nucleosomal binding protein HMGN5 impairs nuclear sturdiness. Nature Communications, 6, 6138. https://doi.org/10.1038/ncomms7138