@article{7bf188420672472a831fe54befc6a890,
title = "AF9 YEATS domain links histone acetylation to DOT1L-mediated H3K79 methylation",
abstract = "The recognition of modified histones by {"}reader{"} proteins constitutes a key mechanism regulating gene expression in the chromatin context. Compared with the great variety of readers for histone methylation, few protein modules that recognize histone acetylation are known. Here, we show that the AF9 YEATS domain binds strongly to histone H3K9 acetylation and, to a lesser extent, H3K27 and H3K18 acetylation. Crystal structural studies revealed that AF9 YEATS adopts an eight-stranded immunoglobin fold and utilizes a serine-lined aromatic {"}sandwiching{"} cage for acetyllysine readout, representing a novel recognition mechanism that is distinct from that of known acetyllysine readers. ChIP-seq experiments revealed a strong colocalization of AF9 and H3K9 acetylation genome-wide, which is important for the chromatin recruitment of the H3K79 methyltransferase DOT1L. Together, our studies identified the evolutionarily conserved YEATS domain as a novel acetyllysine-binding module and established a direct link between histone acetylation and DOT1L-mediated H3K79 methylation in transcription control.",
author = "Yuanyuan Li and Hong Wen and Yuanxin Xi and Kaori Tanaka and Haibo Wang and Danni Peng and Yongfeng Ren and Qihuang Jin and Dent, {Sharon Y.R.} and Wei Li and Haitao Li and Xiaobing Shi",
note = "Funding Information: We thank M. Bedford, J. Bradner, O. Gozani, J. Tyler, and B. Li for comments and reagents. We thank the staffs at beamline BL17U of the Shanghai Synchrotron Radiation Facility and Dr. S. Fan at Tsinghua Center for Structural Biology for their assistance in data collection and the China National Center for Protein Sciences Beijing for providing facility support. We thank the MD Anderson Sequencing and Microarray Facility and the Science Park Next-Generation Sequencing Facility for Solexa sequencing. We thank Joseph Munch for editing the manuscript. This work was supported in part by funds from Welch (G1719) and American Cancer Society (RSG-13-290-01-TBE) to X.S, the Major State Basic Research Development Program in China (2011CB965300) and Program for New Century Excellent Talents in University to H.L., NIH (R01HG007538 to W.L and R01GM067718 to S.Y.R.D), CPRIT (RP110471 to X.S., W.L., and S.Y.R.D), MDACC Institutional Research Grant and Center for Cancer Epigenetics pilot grant to H. Wen, and China Postdoctoral Science Foundation (2014T70069 to Y.L.). Y.L. is a Tsinghua-Peking Center for Life Sciences postdoctoral fellow. W.L. is a recipient of a Duncan Scholar Award. X.S. is a Kimmel Scholar and a R. Lee Clark Fellow. Publisher Copyright: {\textcopyright} 2014 Elsevier Inc.",
year = "2014",
month = oct,
day = "23",
doi = "10.1016/j.cell.2014.09.049",
language = "English (US)",
volume = "159",
pages = "558--571",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "3",
}