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Co-transcriptional histone methylations

机译:共转录组蛋白甲基化

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Genes transcribed by RNA polymerase II show a stereotypicalpattern of histone H3 methylations. H3K4 trimethylationpeaks near the transcription start site, withdimethylation peaking further downstream. H3K36methylation levels increase with distance from the promoter.It is not yet completely understood how this patternis generated, but the mechanism involves directinteractions between the transcribing polymerase and themethyltransferases Set1/COMPASS (for H3K4) and Set2(for H3K36). We are working towards a better understandingof how this coupling works. We are also veryinterested in the function of these co-transcriptionalhistone modifications. Previous work has shown thatmethylated H3K36 recruits the histone deacetylase complexRpd3S and that H3K4me2 recruits the Set3C histonedeacetylase complex. Therefore, a major function of cotranscriptionalhistone methylation is to reset transcribedchromatin to a state less conducive to nucleosome turnover.This pathway represses cryptic promoters inside thetranscribed gene, but also slows transcription elongationthrough this region. We and others have found that thesehistone methylation-deacetylation pathways can be targetedvia overlapping non-coding transcription to regulatenearby promoters. In contrast to H3K4me2 andH3K36me2/3, H3K4me3 correlates with high turnovernucleosomes near transcription start sites. Available datasuggests that H3K4me3 is recognized by three complexescontaining ING/Yng proteins via their PHD fingerdomains. The yeast proteins Yng1 and Yng2 (as well astheir metazoan counterparts) are subunits of histoneacetyltransferase complexes, suggesting that H3K4me3can target histone acetylation. Since acetylation is correlatedwith nucleosome remodeling, this putative pathwaycould be important for gene activation. Surprisingly, thethird Yng protein (Pho23, as well as its metazoan counterparts)is a subunit of the Rpd3L histone deacetylasecomplex, hinting at a more complex series or cycle ofacetylation and deacetylation. We are continuing toprobe the functions of these pathways and some of ourlatest work will be presented.
机译:RNA聚合酶II转录的基因显示出组蛋白H3甲基化的定型模式。 H3K4三甲基化在转录起始位点附近,而二甲基化在下游进一步峰化。 H3K36甲基化水平随与启动子的距离增加而增加。尚未完全了解这种模式的产生方式,但其机制涉及转录聚合酶与甲基转移酶Set1 / COMPASS(对于H3K4)和Set2(对于H3K36)之间的直接相互作用。我们正在努力更好地了解这种耦合的工作方式。我们对这些共转录组蛋白修饰的功能也非常感兴趣。先前的工作表明甲基化的H3K36募集了组蛋白脱乙酰基酶复合物Rpd3S,而H3K4me2募集了Set3C组蛋白脱乙酰基酶复合物。因此,共转录组蛋白甲基化的主要功能是将转录的染色质重置为不利于核小体更新的状态。该途径抑制转录基因内部的隐秘启动子,但也减慢了通过该区域的转录延伸。我们和其他人已经发现,这些组蛋白甲基化-去乙酰化途径可以通过重叠非编码转录来调控附近的启动子而被靶向。与H3K4me2和H3K36me2 / 3相反,H3K4me3与转录起始位点附近的高周转核小体相关。可用数据表明,H3K4me3被三种包含ING / Yng蛋白的复合物通过其PHD指域识别。酵母蛋白Yng1和Yng2(以及它们的后生动物对应物)是组蛋白乙酰转移酶复合物的亚基,表明H3K4me3可以靶向组蛋白乙酰化。由于乙酰化与核小体重塑相关,因此该推定途径对于基因激活可能很重要。令人惊讶地,第三Yng蛋白(Pho23及其后生动物对应物)是Rpd3L组蛋白脱乙酰基酶复合物的亚基,提示乙酰化和脱乙酰基的序列或循环更复杂。我们将继续探索这些途径的功能,并将介绍一些最新的工作。

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