Association of ATRX with pericentric heterochromatin and the Y chromosome of neonatal mouse spermatogonia.
Association of ATRX with pericentric heterochromatin and the Y chromosome of neonatal mouse spermatogonia.
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DOI：
10.1186/1471-2199-9-29
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发表时间：
2008-03-13
影响因子：
--
通讯作者：
De La Fuente R
中科院分区：
文献类型：
--
作者：
Baumann C;Schmidtmann A;Muegge K;De La Fuente R
染色体胞嘧啶甲基化和组蛋白甲基化模式的建立是哺乳动物基因组中异染色质形成所需的关键的表观遗传修饰。然而，针对特定基因组区域的DNA甲基化的初级信号(S)的性质尚不清楚。值得注意的是，组蛋白甲基化和/或染色质重塑蛋白是否在配子发生期间DNA甲基化的建立中发挥作用尚不清楚。小鼠新生精原细胞的染色体显示出一种独特的5-甲基胞嘧啶染色模式，其中着丝粒异染色质是低甲基化的，而染色单体是高度甲基化的。因此，为了深入了解胚系中整体DNA和组蛋白甲基化之间的关系，我们使用新生精原细胞作为模型，以确定这些独特的染色体DNA甲基化模式是否也反映在伴随着组蛋白甲基化的变化中。我们的结果表明，组蛋白H3在赖氨酸9(H3K9me3)三甲基化，这是构成异染色质的标志，以及染色质重塑蛋白ATRX，尽管它们存在广泛的低甲基化，但仍与着丝粒周围的异染色质区域相关。这表明，在新生精原细胞中，染色体5-甲基胞嘧啶模式的调节独立于组蛋白甲基化的变化，这可能反映了维持着丝粒周围异染色质沉默的关键机制。此外，染色质免疫沉淀和荧光原位杂交显示，ATRX和H3K9me3与Y染色体特异的DNA序列结合，装饰Y染色体的两个臂，提示在精子发生过程中该染色体的异染色质和主要的转录静止可能起作用。这些结果与组蛋白修饰和染色质重塑蛋白如ATRX在缺乏5-甲基胞嘧啶的情况下维持构成异染色质结构域转录抑制的作用是一致的，并提供了证据表明，在胚系全基因组表观遗传重编程后，在着丝粒周围异染色质建立和/或维持抑制组蛋白和染色质修饰可能先于建立染色体5-甲基胞嘧啶模式作为新生儿精原细胞的基因组沉默策略。
Establishment of chromosomal cytosine methylation and histone methylation patterns are critical epigenetic modifications required for heterochromatin formation in the mammalian genome. However, the nature of the primary signal(s) targeting DNA methylation at specific genomic regions is not clear. Notably, whether histone methylation and/or chromatin remodeling proteins play a role in the establishment of DNA methylation during gametogenesis is not known. The chromosomes of mouse neonatal spermatogonia display a unique pattern of 5-methyl cytosine staining whereby centromeric heterochromatin is hypo-methylated whereas chromatids are strongly methylated. Thus, in order to gain some insight into the relationship between global DNA and histone methylation in the germ line we have used neonatal spermatogonia as a model to determine whether these unique chromosomal DNA methylation patterns are also reflected by concomitant changes in histone methylation. Our results demonstrate that histone H3 tri-methylated at lysine 9 (H3K9me3), a hallmark of constitutive heterochromatin, as well as the chromatin remodeling protein ATRX remained associated with pericentric heterochromatin regions in spite of their extensive hypo-methylation. This suggests that in neonatal spermatogonia, chromosomal 5-methyl cytosine patterns are regulated independently of changes in histone methylation, potentially reflecting a crucial mechanism to maintain pericentric heterochromatin silencing. Furthermore, chromatin immunoprecipitation and fluorescence in situ hybridization, revealed that ATRX as well as H3K9me3 associate with Y chromosome-specific DNA sequences and decorate both arms of the Y chromosome, suggesting a possible role in heterochromatinization and the predominant transcriptional quiescence of this chromosome during spermatogenesis. These results are consistent with a role for histone modifications and chromatin remodeling proteins such as ATRX in maintaining transcriptional repression at constitutive heterochromatin domains in the absence of 5-methyl cytosine and provide evidence suggesting that the establishment and/or maintenance of repressive histone and chromatin modifications at pericentric heterochromatin following genome-wide epigenetic reprogramming in the germ line may precede the establishment of chromosomal 5-methyl cytosine patterns as a genomic silencing strategy in neonatal spermatogonia.
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影响因子：
30.8
作者：
Gibbons, RJ;McDowell, TL;Higgs, DR
通讯作者：
Higgs, DR
影响因子：
2.6
作者：
Bernardino, J;Lombard, M;Dutrillaux, B
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Dutrillaux, B
影响因子：
2.7
作者：
De La Fuente, R;Viveiros, MM;Eppig, JJ
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Eppig, JJ
影响因子：
64.8
作者：
Jackson, JP;Lindroth, AM;Jacobsen, SE
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Jacobsen, SE
影响因子：
21.3
作者：
De La Fuente, Rabindranath;Baumann, Claudia;Muegge, Kathrin
通讯作者：
Muegge, Kathrin