Nature：蛋白翻译调控网络

　　

生物通报道，加州大学，Fred Hutchinson癌症研究中心以及霍华休斯医学院的科学家近期发现在蛋白翻译的调控机制中，甲基化与组蛋白H2A.Z是一对作用效果相反的调控因子。相关成果公布在11月6日出版的Nature杂志上。

 

真核细胞的染色质可以分为三个区域：第一个区域是通过翻译后组蛋白修饰的功能性区域，第二个是组蛋白变异体区域，第三个是DNA甲基化区域。

 

在动物或是植物体内，甲基化往往是阻止蛋白翻译的过程。正确的甲基化模式是保证真核生物正确发育的关键，而异常的甲基化模式将导致生命体发育异常，在人类来说，常见的癌症甲基化异常就是导致沉默掉肿瘤抑制基因，促使癌症发生。

 

而与甲基化相对的一个生物活性分子是组蛋白变异体H2A.Z，它在基因的5’端接近Swr1 ATPase复合物的位置（这一位置通常是促进蛋白表达的区域）居多。

 

甲基化与变异体组蛋白H2A.Z相对的作用已经被发现，但是两者间的调节机制却一直没被破解。

 

本文的研究者以拟南芥为研究对象，开展这方面的研究。研究者将拟南芥体内的H2A.Z

缺失掉，结果发现甲基化区域的基因表达活性受到抑制。如果MET1 DNA甲基化转移酶发生突变将导致甲基化受抑制， H2A.Z沉积加剧。进一步导致Swr1复合物亚型PIE1发生突变，H2A.Z沉积发生变化，整个基因组会发生超甲基化现象。

 

这些结果表明，如果去除H2A.Z可引起DNA甲基化改变染色质的结构，沉默基因，而H2A.Z具有保护DNA免受甲基化的作用。

 

原文摘要：Histone H2A.Z and DNA methylation are mutually antagonistic chromatin marks

 

【Abstract】

Eukaryotic chromatin is separated into functional domains differentiated by post-translational histone modifications, histone variants and DNA methylation. Methylation is associated with repression of transcriptional initiation in plants and animals, and is frequently found in transposable elements. Proper methylation patterns are crucial for eukaryotic development, and aberrant methylation-induced silencing of tumour suppressor genes is a common feature of human cancer In contrast to methylation, the histone variant H2A.Z is preferentially deposited by the Swr1 ATPase complex near 5' ends of genes where it promotes transcriptional competence. How DNA methylation and H2A.Z influence transcription remains largely unknown. Here we show that in the plant Arabidopsis thaliana regions of DNA methylation are quantitatively deficient in H2A.Z. Exclusion of H2A.Z is seen at sites of DNA methylation in the bodies of actively transcribed genes and in methylated transposons. Mutation of the MET1 DNA methyltransferase, which causes both losses and gains of DNA methylation, engenders opposite changes (gains and losses) in H2A.Z deposition, whereas mutation of the PIE1 subunit of the Swr1 complex that deposits H2A.Z leads to genome-wide hypermethylation. Our findings indicate that DNA methylation can influence chromatin structure and effect gene silencing by excluding H2A.Z, and that H2A.Z protects genes from DNA methylation.

生物通 张欢