Cis- and Trans-acting elements regulate the mouse Psmb9 meiotic recombination hotspot
Cis- and Trans-acting elements regulate the mouse Psmb9 meiotic recombination hotspot
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DOI：
10.1371/journal.pgen.0030100
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发表时间：
2007-06-01
期刊：
影响因子：
4.5
通讯作者：
de Massy, Bernard
中科院分区：
文献类型：
--
作者：
Baudat, Frédéric;de Massy, Bernard
在大多数真核生物中，第一次减数分裂的前期以同源染色体之间高度同源重组为特征。重组事件并不均匀地分布在基因组中，但在局部和大规模上都是不同的。在局部，大多数重组事件聚集在称为热点的短间隔(几千个基数)中，由没有重组或很少重组的大的中间区域隔开。尽管调控重组事件的频率和分布很重要，但控制哺乳动物重组热点活性的遗传因素仍然知之甚少。我们以前通过精子分型鉴定了小鼠主要组织相容性复合体中靠近Psmb9基因的重组热点，证明它是重组的起始部位。为了揭示控制这个起始点活性的一些遗传因素，我们分析了这一热点在雄性和雌性生殖系中，并比较了不同杂交小鼠的重组水平。我们发现一个单倍型特异的元件在距离上和在反式中起作用，在Psmb9处激活约2000倍的重组活性。另一个单倍型特异元件在顺式基因中作用于抑制重组的启动，我们认为这种控制是由于起始区内的多态。此外，我们还描述了与品系和性别差异有关的重组事件的频率和分布的细微变化。这些发现表明，大多数观察到的调节作用于启动水平，并首次分析了小鼠基因组中减数分裂重组热点的活性控制，揭示了位于热点内外的元件的相互作用。
In most eukaryotes, the prophase of the first meiotic division is characterized by a high level of homologous recombination between homologous chromosomes. Recombination events are not distributed evenly within the genome, but vary both locally and at large scale. Locally, most recombination events are clustered in short intervals (a few kilobases) called hotspots, separated by large intervening regions with no or very little recombination. Despite the importance of regulating both the frequency and the distribution of recombination events, the genetic factors controlling the activity of the recombination hotspots in mammals are still poorly understood. We previously characterized a recombination hotspot located close to the Psmb9 gene in the mouse major histocompatibility complex by sperm typing, demonstrating that it is a site of recombination initiation. With the goal of uncovering some of the genetic factors controlling the activity of this initiation site, we analyzed this hotspot in both male and female germ lines and compared the level of recombination in different hybrid mice. We show that a haplotype-specific element acts at distance and in trans to activate about 2,000-fold the recombination activity at Psmb9. Another haplotype- specific element acts in cis to repress initiation of recombination, and we propose this control to be due to polymorphisms located within the initiation zone. In addition, we describe subtle variations in the frequency and distribution of recombination events related to strain and sex differences. These findings show that most regulations observed act at the level of initiation and provide the first analysis of the control of the activity of a meiotic recombination hotspot in the mouse genome that reveals the interactions of elements located both in and outside the hotspot.