GC- and AT-rich chromatin domains differ in conformation and histone modification status and are differentially modulated by Rpd3p.

GC- and AT-rich chromatin domains differ in conformation and histone modification status and are differentially modulated by Rpd3p.
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DOI:
10.1186/gb-2007-8-6-r116
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发表时间:
2007
期刊:
影响因子:
12.3
通讯作者:
Dekker J
Dekker J
中科院分区:
生物学1区
文献类型:
--
作者:
Dekker J

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富含GC和AT的染色质结构域显示出不同的染色质构象,并以组蛋白修饰的不同模式为标志,组蛋白脱乙酰基酶Rpd3p是这些差异的衰减剂。碱基组成在整个基因组中变化,并且与不同结构域中染色体的组织(等粒线)有关。等容区结构域在基因表达水平、复制时间、减数分裂重组水平和染色质结构方面不同。这些差异的分子基础知之甚少。我们已经比较了GC和AT丰富的isochore酵母染色质构象,组蛋白修饰状态和转录。使用3C分析,我们表明,沿着染色体III,GC丰富的等间距线具有染色质结构,其特征在于较低的染色质相互作用频率相比,AT丰富的等间距线,这可能指向一个更广泛的染色质构象。此外,我们发现,在整个基因组中,GC丰富和AT丰富的基因显示不同水平的组蛋白修饰。有趣的是,消除组蛋白去乙酰化酶Rpd3p差异影响GC和AT丰富的结构域的构象。此外,RPD3的缺失激活GC富集基因的表达比AT富集基因更强。组蛋白去乙酰化酶抑制剂Restatin A的作用、Rpd3p结合的全局模式和RPD3缺失对组蛋白H4乙酰化的影响的分析证实,富含GC的染色质的构象和活性对Rpd3p介导的去乙酰化比富含AT的染色质更敏感。我们发现,GC丰富和AT丰富的染色质结构域显示不同的染色质构象,并标记由不同的组蛋白修饰模式。我们确定组蛋白去乙酰化酶Rpd3p作为衰减剂的这些基础组成依赖性的染色质状态的差异。我们提出,GC丰富的染色质结构域往往发生在一个更活跃的构象和Rpd3p活性抑制这种倾向在整个基因组。
GC-rich and AT-rich chromatin domains display distinct chromatin conformations and are marked by distinct patterns of histone modifications, and the histone deacetylase Rpd3p is an attenuator of these differences. Base-composition varies throughout the genome and is related to organization of chromosomes in distinct domains (isochores). Isochore domains differ in gene expression levels, replication timing, levels of meiotic recombination and chromatin structure. The molecular basis for these differences is poorly understood. We have compared GC- and AT-rich isochores of yeast with respect to chromatin conformation, histone modification status and transcription. Using 3C analysis we show that, along chromosome III, GC-rich isochores have a chromatin structure that is characterized by lower chromatin interaction frequencies compared to AT-rich isochores, which may point to a more extended chromatin conformation. In addition, we find that throughout the genome, GC-rich and AT-rich genes display distinct levels of histone modifications. Interestingly, elimination of the histone deacetylase Rpd3p differentially affects conformation of GC- and AT-rich domains. Further, deletion of RPD3 activates expression of GC-rich genes more strongly than AT-rich genes. Analyses of effects of the histone deacetylase inhibitor trichostatin A, global patterns of Rpd3p binding and effects of deletion of RPD3 on histone H4 acetylation confirmed that conformation and activity of GC-rich chromatin are more sensitive to Rpd3p-mediated deacetylation than AT-rich chromatin. We find that GC-rich and AT-rich chromatin domains display distinct chromatin conformations and are marked by distinct patterns of histone modifications. We identified the histone deacetylase Rpd3p as an attenuator of these base composition-dependent differences in chromatin status. We propose that GC-rich chromatin domains tend to occur in a more active conformation and that Rpd3p activity represses this propensity throughout the genome.
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发表时间: 2003-05-27
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发表时间: 2002-12-13
期刊: CELL
影响因子: 64.5
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DOI: 10.1101/gr.5571506
发表时间: 2006-10-01
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影响因子: 7
作者:
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通讯作者: Dekker, Job