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Dot1 binding induces chromatin rearrangements by histone methylation-dependent and -independent mechanisms

机译:Dot1结合通过组蛋白甲基化依赖性和非依赖性机制诱导染色质重排

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Background Methylation of histone H3 lysine 79 (H3K79) by Dot1 is highly conserved among species and has been associated with both gene repression and activation. To eliminate indirect effects and examine the direct consequences of Dot1 binding and H3K79 methylation, we investigated the effects of targeting Dot1 to different positions in the yeast genome. Results Targeting Dot1 did not activate transcription at a euchromatic locus. However, chromatin-bound Dot1 derepressed heterochromatin-mediated gene silencing over a considerable distance. Unexpectedly, Dot1-mediated derepression was established by both a H3K79 methylation-dependent and a methylation-independent mechanism; the latter required the histone acetyltransferase Gcn5. By monitoring the localization of a fluorescently tagged telomere in living cells, we found that the targeting of Dot1, but not its methylation activity, led to the release of a telomere from the repressive environment at the nuclear periphery. This probably contributes to the activity-independent derepression effect of Dot1. Conclusions Targeting of Dot1 promoted gene expression by antagonizing gene repression through both histone methylation and chromatin relocalization. Our findings show that binding of Dot1 to chromatin can positively affect local gene expression by chromatin rearrangements over a considerable distance.
机译:背景Dot1对组蛋白H3赖氨酸79(H3K79)的甲基化在物种之间高度保守,并且与基因阻抑和激活有关。为了消除间接影响并检查Dot1结合和H3K79甲基化的直接后果,我们研究了将Dot1靶向酵母基因组中不同位置的影响。结果靶向Dot1不能激活常染色体上的转录。但是,与染色质结合的Dot1在相当长的距离内抑制了异染色质介导的基因沉默。出乎意料的是,通过H3K79甲基化依赖性和甲基化依赖性机制建立了Dot1介导的抑制作用。后者需要组蛋白乙酰转移酶Gcn5。通过监测荧光标记的端粒在活细胞中的定位,我们发现以Dot1为靶标而不是其甲基化活性导致了端粒从核环境的阻抑环境中释放出来。这可能有助于Dot1的活动无关的抑制作用。结论以Dot1为靶标可通过拮抗组蛋白甲基化和染色质重新定位来抑制基因阻抑而促进基因表达。我们的发现表明Dot1与染色质的结合可以通过相当长的距离上的染色质重排而积极影响局部基因的表达。

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