拟南芥组蛋白H3乙酰化与H3K9甲基化修饰之交互作用在基因表达调控过程的机制研究

In eukaryotic cells, histone posttranslational modifications (PTMs) can regulate chromatin structure directly and frequently act as binding sites for the recruitment of other non-histone proteins to chromatin, and there are many combinations of modifications that are either more likely to occur together, or are mutually exclusive, suggesting cross-talk between these marks. However, less is known about the cross-talk between different PTMs in plants. In this study, we found the interaction between the histone deacetylase HDA6 and histone H3K9 methyltransferase SUVHs in Arabidopsis, indicating that there is a cross-talk between histone deacetylation and H3K9 methylation. To better understand the mechanisms of this cross-talk, we will analyze the histone acetylation substrates of HDA6 in in vivo and vitro. In addition, how HDA6-mediated H3 deacetylation affects SUVHs-mediated H3K9 metylation and how this cross-talk regulates the target genes of HDA6 and SUVHs will also be investigated. This study will contribute to our understanding of molecular mechanisms underlying the cross-talk between different PTMs in plants and provide insights into epigenetic regulation in gene regulation in plants.

组蛋白翻译后修饰（post translational modifications, PTMs）往往通过不同的PTMs之间的cross-talk参与真核生物特异的生理过程。然而对植物PTMs之间的cross-talk的方式和作用机制并不清楚。本项目在发现拟南芥组蛋白去乙酰化酶HDA6与组蛋白H3K9甲基转移酶SUVHs相互作用的基础上拟开展如下研究：1）通过体内、外手段研究HDA6在组蛋白H3上的特异作用位点；2）研究HDA6介导的H3ac如何影响SUVHs介导的H3K9me修饰；3）H3ac与H3K9me修饰之间的cross-talk如何调控HDA6和SUVHs靶基因。通过上述研究，阐明HDA6介导的H3ac和SUVHs介导的H3K9me之间cross-talk如何调控基因转录以及作用机制。

组蛋白翻译后修饰（post translational modifications, PTMs）往往通过不同的PTM.s之间的cross-talk参与真核生物特异的生理过程。然而对植物PTMs之间的cross-talk的方式和作用机制并不清楚。本项目取得了如下研究结果：(1) HDA6与组蛋白甲基转移酶SUVH4、5和6相互作用，通过调控转座子组蛋白的乙酰化和H3K9me2水平共同调控转座子的表达。另外，质谱鉴定发现HDA6 S427和S429残基存在磷酸化修饰，该修饰对HDA6与SUVH5相互作用和HDA6的酶活性至关重要。(2) H3K9去甲基化酶JMJ28与FBH转录因子相互作用，通过去除抑制标记H3K9me2来激活CO。在fbh四突变体中，JMJ28在CO基因座上的占有率降低，表明JMJ28的结合依赖于FBH。此外，全基因组占用谱分析表明JMJ28与基因组的结合与FBH3的结合重叠，表明JMJ28和FBH3的功能关联。拟南芥JMJ28通过与FBH转录因子相互作用以从CO基因座中去除H3K9me2，从而起到CO激活剂的作用。(3) 染色质重塑ATP酶BRAHMA与GATA家族转录因子GNC相互作用，通过降低H3K4me3和增加拟南芥开花期间SOC1基因座的DNA甲基化水平直接抑制SOC1的表达。本项目所取的研究结果将为全面解析组蛋白各PTMs之间的cross-talk的分子机制奠定基础，同时在植物中首次系统开展组蛋白乙酰化和甲基化之间的cross-talk研究有利于拓展我们对基因表达表观遗传调节的认识。