Chromatin decompaction by the nucleosomal binding protein HMGN5 impairs nuclear sturdiness

作者：Takashi Furusawa, Mark Rochman, Leila Taher, Emilios K. Dimitriadis, Kunio Nagashima, Stasia A. Anderson, Michael Bustin · 发表于：Nature Communications · 年份：2015 · DOI：10.1038/ncomms7138 · 被引用次数：157 · 研究领域：Genomics and Chromatin Dynamics、RNA Research and Splicing、Nuclear Structure and Function

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. Whether heterochromatin affects the physical properties of the nucleus is not known. Here, Furusawa et al. show that chromatin decompaction decreases the sturdiness of the nucleus in cultured cells and leads to lamina disruption and cardiac abnormalities in adult mice, suggesting a structural, non-genetic function for heterochromatin.