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
Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center for Life Sciences, Peking University Health Science Center, Beijing 100191, China; Department of Radiation Oncology, Weill Medical College of Cornell University, New York, NY 10065, USA.
Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center for Life Sciences, Peking University Health Science Center, Beijing 100191, China.
Cell Rep. 2014 Sep 25;8(6):2003-2014. doi: 10.1016/j.celrep.2014.08.008. Epub 2014 Sep 4.
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.
染色质的组织和动态变化是全球基因转录所不可或缺的。组蛋白修饰影响染色质状态和基因表达。PTEN在肿瘤抑制、发育和代谢中发挥多种作用。在此，我们报告PTEN、组蛋白H1和染色质之间的相互作用。我们发现PTEN的缺失导致组蛋白H1从染色质上解离以及染色质的解聚。PTEN的缺失还导致赖氨酸16处组蛋白H4乙酰化水平升高，这是染色质激活的一种表观遗传标记。我们发现PTEN和组蛋白H1通过它们的C末端结构域发生物理相互作用。PTEN C末端的破坏促进了MOF乙酰转移酶与染色质的结合并诱导H4K16乙酰化。H4K16的过度乙酰化损害了PTEN与组蛋白H1的结合，这构成了可能降低染色质稳定性的调节反馈。我们的结果表明PTEN控制染色质凝聚，从而影响基因表达。我们提出PTEN通过组蛋白和染色质重塑来调节全球基因转录谱。
