Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom.
Genes Dev. 2010 Apr 1;24(7):647-52. doi: 10.1101/gad.1881710. Epub 2010 Mar 18.
Chromodomain proteins (Chp1/Chp2/Swi6/Clr4) bind to methylated H3K9 (H3K9me) and regulate pericentric heterochromatin in fission yeast. Chp1 and Clr4 (H3K9-HMT), bind transcriptionally active heterochromatin, whereas Chp2/Swi6 (HP1 homologs) are recruited during the inactive state. We show that H3K4 acetylation (H3K4ac) plays a role in the transition of dimethylated H3K9 (H3K9me2) occupancy from Chp1/Clr4 to Chp2/Swi6. H3K4ac, mediated by Mst1, is enriched at pericentromeres concomitantly with heterochromatin reassembly. H3K4R (Lys --> Arg) mutation increases Chp1 and decreases Chp2/Swi6 pericentric occupancy and exhibits centromeric desilencing. Consistent with structural data, H3K4ac specifically reduces Chp1/Clr4 affinity to H3K9me. We propose that H3K4ac mediates a chromodomain switch from Chp1/Clr4 to Swi6/Chp2 to allow heterochromatin reassembly.
染色质域蛋白（Chp1/Chp2/Swi6/Clr4）结合甲基化的 H3K9（H3K9me）并调节裂殖酵母的着丝粒异染色质。Chp1 和 Clr4（H3K9-HMT）结合转录活跃的异染色质，而 Chp2/Swi6（HP1 同源物）在非活性状态下被招募。我们表明 H3K4 乙酰化（H3K4ac）在二甲基化 H3K9（H3K9me2）占有率从 Chp1/Clr4 向 Chp2/Swi6 的转变中起作用。由 Mst1 介导的 H3K4ac 富集在着丝粒周围，与异染色质重新组装同时发生。H3K4R（Lys --> Arg）突变增加了 Chp1 并减少了 Chp2/Swi6 着丝粒占有率，并表现出着丝粒去沉默。与结构数据一致，H3K4ac 特异性降低了 Chp1/Clr4 对 H3K9me 的亲和力。我们提出 H3K4ac 介导染色质域从 Chp1/Clr4 到 Swi6/Chp2 的转换，以允许异染色质重新组装。
