@article{f5684453389f498c8e4483c82ca28bda,
title = "ZMYND8 Reads the Dual Histone Mark H3K4me1-H3K14ac to Antagonize the Expression of Metastasis-Linked Genes",
abstract = "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{\textquoteright}s PHD-Bromo cassette couples H3K4me1-H3K14ac with downregulation of metastasis-linked genes.",
author = "Na Li and Yuanyuan Li and Jie Lv and Xiangdong Zheng and Hong Wen and Hongjie Shen and Guangjing Zhu and Chen, {Tsai Yu} and Dhar, {Shilpa S.} and Kan, {Pu Yeh} and Zhibin Wang and Ramin Shiekhattar and Xiaobing Shi and Fei Lan and Kaifu Chen and Wei Li and Haitao Li and Lee, {Min Gyu}",
note = "Funding Information: We are thankful to Dr. Zhenbo Han and Mr. Su Zhang for their technical assistance and to Drs. Chunru Lin and Liuqing Yang for their reagents. We thank the staff at beamline BL17U of the Shanghai Synchrotron Radiation Facility and the China National Center for Protein Sciences Beijing for providing facility support. This study was supported by grants to M.G.L. from the NIH (R01 CA157919 and R01 GM095659) and the Cancer Prevention and Research Institute of Texas (CPRIT) (RP110183), to H.L. from the Ministry of Science and Technology of China (2016YFA0500700) and the Tsinghua University Initiative Scientific Research Program, to X.S. from the Welch foundation (G1719) and CPRIT (RP110471 and RP140323), to Z.W. from the NIH (ES025761), to Y.L. from the National Natural Science Foundation of China (31400633) and China Postdoctoral Science Foundation (2014T70069), to W.L. from the NIH (R01 HG007538) and CPRIT (RP110471), and to R.S. from the NIH (R01 GM078455 and R01 GM105754) and Sylvester Comprehensive Cancer Center at University of Miami Health System. N.L. was supported by a postdoctoral fellowship from the Center for Cancer Epigenetics at the MD Anderson Cancer Center. Y.L. was supported by a Tsinghua Advanced Innovation fellowship from the Beijing Advanced Innovation Center for Structural Biology at Tsinghua University. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = aug,
day = "4",
doi = "10.1016/j.molcel.2016.06.035",
language = "English (US)",
volume = "63",
pages = "470--484",
journal = "Molecular cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "3",
}