Dot1 binding induces chromatin rearrangements by histone methylation-dependent and -independent mechanisms.
Dot1 binding induces chromatin rearrangements by histone methylation-dependent and -independent mechanisms.
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DOI：
10.1186/1756-8935-4-2
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发表时间：
2011-02-03
影响因子：
3.9
通讯作者：
van Leeuwen F
中科院分区：
文献类型：
--
作者：
Stulemeijer IJ;Pike BL;Faber AW;Verzijlbergen KF;van Welsem T;Frederiks F;Lenstra TL;Holstege FC;Gasser SM;van Leeuwen F
组蛋白H3赖氨酸79（H3 K79）的甲基化是高度保守的物种之间，并已与基因抑制和激活。为了消除间接影响并检查Dot 1结合和H3 K79甲基化的直接后果，我们研究了将Dot 1靶向酵母基因组中不同位置的影响。靶向Dot 1没有激活常染色质位点的转录。然而，染色质结合的Dot 1去阻遏异染色质介导的基因沉默在相当长的距离。出乎意料的是，Dot 1介导的去阻遏是通过H3 K79甲基化依赖性和甲基化独立性机制建立的;后者需要组蛋白乙酰转移酶Gcn 5。通过监测活细胞中荧光标记的端粒的定位，我们发现Dot 1的靶向，而不是其甲基化活性，导致端粒从核周边的压抑环境中释放。这可能有助于Dot 1的活性独立的去阻遏作用。靶向Dot 1通过组蛋白甲基化和染色质重定位来拮抗基因抑制，从而促进基因表达。我们的研究结果表明，Dot 1与染色质的结合可以通过染色质重排在相当长的距离内对局部基因表达产生积极影响。
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. 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. 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.
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DOI：
10.1073/pnas.0909169107
发表时间：
2010-03-23
影响因子：
11.1
作者：
Ehrentraut, Stefan;Weber, Jan M.;Ehrenhofer-Murray, Ann E.
通讯作者：
Ehrenhofer-Murray, Ann E.
影响因子：
3.3
作者：
Gardner, R;Cronin, S;Hampton, R
通讯作者：
Hampton, R
影响因子：
16.8
作者：
Frederiks, Floor;Tzouros, Manuel;van Leeuwen, Fred
通讯作者：
van Leeuwen, Fred
影响因子：
16
作者：
Altaf, Mohammed;Utley, Rhea T.;Cote, Jacques
通讯作者：
Cote, Jacques
影响因子：
4
作者：
Dieppois, Guennaelle;Stutz, Francoise
通讯作者：
Stutz, Francoise