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Crystal structure of AF9 YEATS bound to H3K9ac peptide
Structural highlights
DiseaseAF9_HUMAN A chromosomal aberration involving MLLT3 is associated with acute leukemias. Translocation t(9;11)(p22;q23) with KMT2A/MLL1. The result is a rogue activator protein. FunctionAF9_HUMAN Component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA.[1] [2] Publication Abstract from PubMedThe 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. AF9 YEATS Domain Links Histone Acetylation to DOT1L-Mediated H3K79 Methylation.,Li Y, Wen H, Xi Y, Tanaka K, Wang H, Peng D, Ren Y, Jin Q, Dent SY, Li W, Li H, Shi X Cell. 2014 Oct 23;159(3):558-71. doi: 10.1016/j.cell.2014.09.049. PMID:25417107[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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