PTEN Interacts with Histone H1 and Controls Chromatin Condensation

• Published in: Cell reports (Cambridge) 2014-09, Vol.8 (6), p.2003-2014
• Main Authors: Chen, Zhu Hong, Zhu, Minglu, Yang, Jingyi, Liang, Hui, He, Jinxue, He, Shiming, Wang, Pan, Kang, Xi, McNutt, Michael A., Yin, Yuxin, Shen, Wen H.
• Format: Article
• Language: English
• Subjects: Acetylation; Animals; Cell Line; Chromatin - metabolism; Chromosomal Proteins, Non-Histone - metabolism; Gene Expression Profiling; Histones - chemistry; Histones - genetics; Histones - metabolism; Mice; Promoter Regions, Genetic; Protein Binding; Protein Structure, Tertiary; PTEN Phosphohydrolase - deficiency; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2014.08.008

Chromatin organization and dynamics are integral to global gene transcription. Histone modification influences chromatin status and gene expression. PTEN plays multiple roles in tumor suppression, development, and metabolism. Here, we report on the interplay of PTEN, histone H1, and chromatin. We show that loss of PTEN leads to dissociation of histone H1 from chromatin and decondensation of chromatin. PTEN deletion also results in elevation of histone H4 acetylation at lysine 16, an epigenetic marker for chromatin activation. We found that PTEN and histone H1 physically interact through their C-terminal domains. Disruption of the PTEN C terminus promotes the chromatin association of MOF acetyltransferase and induces H4K16 acetylation. Hyperacetylation of H4K16 impairs the association of PTEN with histone H1, which constitutes regulatory feedback that may reduce chromatin stability. Our results demonstrate that PTEN controls chromatin condensation, thus influencing gene expression. We propose that PTEN regulates global gene transcription profiling through histones and chromatin remodeling. [Display omitted] •PTEN maintains chromatin condensation through interaction with histone H1•The PTEN C terminus is required for its interplay with histones and chromatin•Loss of PTEN or the PTEN C terminus causes H1 displacement and H4K16 acetylation•H4K16 hyperacetylation weakens the interaction between PTEN and histone H1 This study reveals a function of PTEN tumor suppressor in global transcriptional regulation through control of chromatin remodeling. Chen et al. demonstrate that PTEN physically associates with histone H1 to maintain a condensed chromatin structure, manifested by chromatin occupancy of linker histone H1 and by hypoacetylation of histone H4, leading to repression of overall gene activity. Loss of PTEN or its C terminus triggers a positive feedback regulatory loop between H4K16 hyperacetylation and impairment of PTEN-H1 interaction to facilitate abnormal chromatin decondensation and gene activation.