xnd-1 regulates the global recombination landscape in Caenorhabditis elegans.

xnd-1 regulates the global recombination landscape in Caenorhabditis elegans.
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DOI:
10.1038/nature09429
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发表时间:
2010-10-14
期刊:
影响因子:
64.8
通讯作者:
--
中科院分区:
综合性期刊1区
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减数分裂交叉(CO)重组建立了同源染色体之间的物理联系,这是它们正确分离到发育配子所必需的,并通过在亲本染色体之间改组遗传物质来促进遗传多样性。COS需要形成双链断裂(DSB)来产生用于链交换的底物。DSB在称为热点的小间隔内发生,并且在个人之间和个人之间存在着热点使用的显著差异。这种变异被认为反映了序列同一性和染色质结构、DNA拓扑和/或染色体结构域组织的差异。染色体表现出不同的不分离频率(NDJ),反映了减数分裂交叉控制的内在差异,但这些差异的潜在基础仍然不清楚。在这里,我们证明了一种新的染色质因子,X非分离因子1(XND-1),负责COS在线虫中的全球分布。XND-1也是在X上形成双链断裂(DSB)所必需的,但令人惊讶的是,XND-1蛋白是常染色体富含的。我们证明了XND-1的功能独立于X染色体特异基因沉默所需的基因,揭示了一条区分X与胚系常染色体的新途径,并进一步表明XND-1至少部分地通过调节H_2A赖氨酸5乙酰化水平而对Cos发挥作用。
Meiotic crossover (CO) recombination establishes physical linkages between homologous chromosomes that are required for their proper segregation into developing gametes and promotes genetic diversity by shuffling genetic material between parental chromosomes. COs require the formation of double strand breaks (DSBs) to create the substrate for strand exchange. DSBs occur in small intervals called hotspots and significant variation in hotspot usage exists between and among individuals. This variation is thought to reflect differences in sequence identity and chromatin structure, DNA topology and/ or chromosome domain organization. Chromosomes show different frequencies of nondisjunction (NDJ), reflecting inherent differences in meiotic crossover control, yet the underlying basis of these differences remains elusive. Here we show that a novel chromatin factor, X non-disjunction factor 1 (xnd-1), is responsible for the global distribution of COs in C. elegans. xnd-1 is also required for formation of double-strand breaks (DSBs) on the X, but surprisingly XND-1 protein is autosomally-enriched. We show that xnd-1 functions independently of genes required for X chromosome-specific gene silencing, revealing a novel pathway that distinguishes the X from autosomes in the germ line, and further show that xnd-1 exerts its effects on COs, at least in part, by modulating levels of H2A lysine 5 acetylation.
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