Histone hypoacetylation is required to maintain late replication timing of constitutive heterochromatin.
Histone hypoacetylation is required to maintain late replication timing of constitutive heterochromatin.
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DOI：
10.1093/nar/gkr723
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发表时间：
2012-01
影响因子：
14.9
通讯作者：
Cardoso MC
中科院分区：
文献类型：
--
作者：
Casas-Delucchi CS;van Bemmel JG;Haase S;Herce HD;Nowak D;Meilinger D;Stear JH;Leonhardt H;Cardoso MC
基因组的复制是一个时空高度组织化的过程。然而，它在整个发育过程中的灵活性表明，这一过程不受基因调控。然而，控制复制时间的机制和染色质修饰仍然不清楚。我们利用突出的结构和定义异染色质景观的臂间区域作为一个例子，后期复制组成异染色质。我们操纵这些区域的主要染色质标记，即组蛋白乙酰化，DNA和组蛋白甲基化，以及染色质凝聚，并确定这些改变的染色质状态对复制时间的影响。在这里，我们表明，DNA和组蛋白甲基化以及乙酰化水平的操纵引起大规模的异染色质去凝聚。然而，组蛋白去甲基化和随之而来的去凝聚并不影响复制的时间。相反，免疫荧光原位杂交和延时分析表明，降低DNA甲基化，以及增加组蛋白乙酰化，提前异染色质复制的开始。虽然dnmt 1 −/−细胞在染色中心显示组蛋白乙酰化增加，但组蛋白超乙酰化并不诱导DNA去甲基化。因此，我们认为组蛋白低乙酰化是维持正常异染色质复制动力学所必需的。我们推测，一个高水平的组蛋白乙酰化可能会增加发射效率的起源，并伴随着，先进的复制时间的不同的基因组区域。
The replication of the genome is a spatio-temporally highly organized process. Yet, its flexibility throughout development suggests that this process is not genetically regulated. However, the mechanisms and chromatin modifications controlling replication timing are still unclear. We made use of the prominent structure and defined heterochromatic landscape of pericentric regions as an example of late replicating constitutive heterochromatin. We manipulated the major chromatin markers of these regions, namely histone acetylation, DNA and histone methylation, as well as chromatin condensation and determined the effects of these altered chromatin states on replication timing. Here, we show that manipulation of DNA and histone methylation as well as acetylation levels caused large-scale heterochromatin decondensation. Histone demethylation and the concomitant decondensation, however, did not affect replication timing. In contrast, immuno-FISH and time-lapse analyses showed that lowering DNA methylation, as well as increasing histone acetylation, advanced the onset of heterochromatin replication. While dnmt1−/− cells showed increased histone acetylation at chromocenters, histone hyperacetylation did not induce DNA demethylation. Hence, we propose that histone hypoacetylation is required to maintain normal heterochromatin duplication dynamics. We speculate that a high histone acetylation level might increase the firing efficiency of origins and, concomitantly, advances the replication timing of distinct genomic regions.
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影响因子：
3.1
作者：
Muck, Joscha;Zink, Daniele
通讯作者：
Zink, Daniele
影响因子：
9.2
作者：
Lin, CM;Fu, HQ;Aladjem, MI
通讯作者：
Aladjem, MI
使用超分辨率光显微镜在纳米尺度上测量复制结构。
影响因子：
14.9
作者：
Baddeley D;Chagin VO;Schermelleh L;Martin S;Pombo A;Carlton PM;Gahl A;Domaing P;Birk U;Leonhardt H;Cremer C;Cardoso MC
通讯作者：
Cardoso MC
DOI：
10.1083/jcb.149.2.271
发表时间：
2000-04-17
期刊：
The Journal of cell biology
影响因子：
--
作者：
Leonhardt H;Rahn HP;Weinzierl P;Sporbert A;Cremer T;Zink D;Cardoso MC
通讯作者：
Cardoso MC
DOI：
10.1007/s10577-008-9005-y
发表时间：
2009
期刊：
Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology
影响因子：
--
作者：
Popova EY;Krauss SW;Short SA;Lee G;Villalobos J;Etzell J;Koury MJ;Ney PA;Chasis JA;Grigoryev SA
通讯作者：
Grigoryev SA