Carnegie Institution of Washington, Department of Embryology, Baltimore, Maryland 21218, USA.
Nature. 2010 Oct 14;467(7317):839-43. doi: 10.1038/nature09429.
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.
减数分裂交叉（CO）重组在同源染色体之间建立物理连接，这是它们正确分离到发育中的配子所必需的，并通过在亲本染色体之间交换遗传物质来促进遗传多样性。CO 需要形成双链断裂（DSB），为链交换创造底物。DSB 发生在称为热点的小间隔中，个体之间和个体内部的热点使用存在显著差异。这种差异被认为反映了序列同一性和染色质结构、DNA 拓扑结构和/或染色体结构域组织的差异。染色体表现出不同的非分离（NDJ）频率，反映了减数分裂 CO 控制的固有差异，但这些差异的潜在基础仍然难以捉摸。在这里，我们表明一种新型染色质因子 X 非分离因子 1（xnd-1）负责秀丽隐杆线虫 CO 的全局分布。xnd-1 也需要在 X 上形成双链断裂（DSB），但令人惊讶的是，XND-1 蛋白在常染色体上富集。我们表明，xnd-1 独立于 X 染色体特异性基因沉默所需的基因发挥作用，揭示了一种新的途径，将 X 与生殖系中的常染色体区分开来，并进一步表明 xnd-1 通过调节 H2A 赖氨酸 5 乙酰化水平至少部分地对 CO 发挥作用。
