title: PTEN interacts with histone H1 and controls chromatin condensation.
abstract: 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.
authors.affiliation: 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.
authors.forename: Zhu Hong
authors.initials: ZH
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Minglu
authors.initials: M
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Hui
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Radiation Oncology, Weill Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Jinxue
authors.initials: J
authors.lastname: He
authors.affiliation: 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.
authors.forename: Shiming
authors.initials: S
authors.lastname: He
authors.affiliation: 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.
authors.forename: Pan
authors.initials: P
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Xi
authors.initials: X
authors.lastname: Kang
authors.affiliation: 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.
authors.forename: Michael A
authors.initials: MA
authors.lastname: McNutt
authors.affiliation: 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. Electronic address: yinyuxin@hsc.pku.edu.cn.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Radiation Oncology, Weill Medical College of Cornell University, New York, NY 10065, USA. Electronic address: wes2007@med.cornell.edu.
authors.forename: Wen H
authors.initials: WH
authors.lastname: Shen
mesh_terms: D000107:Acetylation; D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D020869:Gene Expression Profiling; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D000090266:Chromobox Protein Homolog 5; D051059:PTEN Phosphohydrolase