Science2014-06-11 2:02 PM

“组蛋白密码”揭开基因活性是如何保持之谜 Selective Methylation of Histone H3 Variant H3.1 Regulates Heterochromatin Replication

论文摘要 

在植物中,异染色质—或紧凑排列的DNA—上的一个叫做H3K27me1的特别标记在细胞分裂时必须得到保守,这样其子细胞才能接受有着相似组织的DNA。

如今,一项由Yannick Jacob及其同事所做的新的研究显示,在ATXR5和ATXR6之间的特别的相互作用以及一个被称作H3.1的组蛋白变异体在拟南芥中维持着这一关键性的H3K27me1标志;ATXR5 和 ATXR6是修饰组蛋白的2个酶,而组蛋白是将DNA装入异染色质的蛋白。

研究人员以2.1埃的分辨率弄清楚了与 H3.1 肽形成复合物的ATXR5的晶体结构,而它显示了为什么与不依赖于复制的H3.3变异体相比,ATXR5酶更倾向于依赖复制的 H3.1变异体。他们的发现证明了组蛋白变异体是如何通过控制能够重新塑造在细胞核中的异染色质的酶来指示基因表达的后生变化的。

他们还为异染色质上的H3K27me1标志的有丝分裂遗传提供了一个简单的模型,且他们帮助解释了为什么富集有H3.3的基因会在动植物中随着进化时间的推移而一直得到如此好的保存。

Abstract 

Histone variants have been proposed to act as determinants for posttranslational modifications with widespread regulatory functions. We identify a histone-modifying enzyme that selectively methylates the replication-dependent histone H3 variant H3.1. The crystal structure of the SET domain of the histone H3 lysine-27 (H3K27) methyltransferase ARABIDOPSIS TRITHORAX-RELATED PROTEIN 5 (ATXR5) in complex with a H3.1 peptide shows that ATXR5 contains a bipartite catalytic domain that specifically “reads” alanine-31 of H3.1. Variation at position 31 between H3.1 and replication-independent H3.3 is conserved in plants and animals, and threonine-31 in H3.3 is responsible for inhibiting the activity of ATXR5 and its paralog, ATXR6. Our results suggest a simple model for the mitotic inheritance of the heterochromatic mark H3K27me1 and the protection of H3.3-enriched genes against heterochromatization during DNA replication.

Editor's Summary

Making a Histone Mark

The covalent marks on histones (the principal components of chromatin) play a critical role in the regulation of gene expression. Somehow these marks are preserved when a cell in a tissue divides so that the daughter cells maintain the gene expression program and tissue identity of the parent cell. Jacob et al. (p. 1249) show that the Arabidopsis histone methylase ATXR5 is specific for the replication-dependent histone variant H3.1 and maintains the repressive histone H3 lysine-27 methyl mark on the H3.1 variant during genome replication, thus, preserving cell-type–specific regions of heterochromatin and gene repression through cell division and beyond.

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