Chromatin decompaction by the nucleosomal binding protein HMGN5 impairs nuclear sturdiness

Nat Commun. 2015 Jan 22:6:6138. doi: 10.1038/ncomms7138.

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.

Publication types

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

MeSH terms

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

Substances

  • HMGN Proteins
  • Heterochromatin
  • Histones
  • Hmgn5 protein, mouse
  • Lamin Type B
  • Cre recombinase
  • Integrases