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ZMYND8 Reads the Dual Histone Mark H3K4me1-H3K14ac to Antagonize the Expression of Metastasis-Linked Genes.

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机构： [1]Department of Molecular and Cellular Oncology, The University of TexasMDAnderson Cancer Center, 1515 Holcombe Boulevard, Houston,TX 77030, USA [2]MOEKey Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences,School of Medicine, Beijing 100084, China [3]Tsinghua-Peking Center for Life SciencesTsinghua University, Beijing 100084, China [4]Institute for Academic Medicine, Department of Cardiovascular SciencesThe Methodist Hospital Research Institute, Houston, TX 77030, USA [5]Center for Cardiovascular Regeneration, Department of Cardiovascular SciencesThe Methodist Hospital Research Institute, Houston, TX 77030, USA [6]Weill Cornell Medical College, Cornell University, New York, NY 10065, USA [7]Department of Epigenetics and Molecular Carcinogenesis, The University of TexasMDAnderson Cancer Center, 1515 Holcombe Boulevard,Houston, TX 77030, USA [8]Key Laboratory of Epigenetics, Institutes of Biomedical Sciences and Key Laboratory of Birth Defect, Children’s Hospital, Fudan University,Shanghai 201102, China [9]Department of Environmental Health Sciences, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore,MD 21205, USA [10]University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Department of Human Genetics,Biomedical Research Building, 1501 NW 10th Avenue, Miami, FL 33136, USA [11]Division of Biostatistics, Dan L. Duncan Cancer Center, and Department of Molecular and Cellular Biology, Baylor College of Medicine,One Baylor Plaza, Houston, TX 77030, USA [12]Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [13]Cancer Biology Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA

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Histone acetylation, including acetylated H3K14 (H3K14ac), is generally linked to gene activation. Monomethylated histone H3 lysine 4 (H3K4me1), together with other gene-activating marks, denotes active genes. In contrast to usual gene-activating functions of H3K14ac and H3K4me1, we here show that the dual histone modification mark H3K4me1-H3K14ac is recognized by ZMYND8 (also called RACK7) and can function to counteract gene expression. We identified ZMYND8 as a transcriptional corepressor of the H3K4 demethylase JARID1D. ZMYND8 antagonized the expression of metastasis-linked genes, and its knockdown increased the cellular invasiveness in vitro and in vivo. The plant homeodomain (PHD) and Bromodomain cassette in ZMYND8 mediated the combinatorial recognition of H3K4me1-H3K14ac and H3K4me0-H3K14ac by ZMYND8. These findings uncover an unexpected role for the signature H3K4me1-H3K14ac in attenuating gene expression and reveal a metastasis-suppressive epigenetic mechanism in which ZMYND8's PHD-Bromo cassette couples H3K4me1-H3K14ac with downregulation of metastasis-linked genes. Copyright © 2016 Elsevier Inc. All rights reserved.

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出版当年[2016]版：

大类 | 1 区

生物

小类 | 1 区生化与分子生物学 1 区细胞生物学

最新[2023]版：

大类 | 1 区

生物学

小类 | 1 区生化与分子生物学 1 区细胞生物学

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第一作者机构： [1]Department of Molecular and Cellular Oncology, The University of TexasMDAnderson Cancer Center, 1515 Holcombe Boulevard, Houston,TX 77030, USA

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通讯机构： [1]Department of Molecular and Cellular Oncology, The University of TexasMDAnderson Cancer Center, 1515 Holcombe Boulevard, Houston,TX 77030, USA [2]MOEKey Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences,School of Medicine, Beijing 100084, China [3]Tsinghua-Peking Center for Life SciencesTsinghua University, Beijing 100084, China [12]Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [13]Cancer Biology Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA

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