A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis
A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis
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DOI：
10.7554/e.life.28383
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发表时间：
2017-10-26
期刊：
影响因子：
7.7
通讯作者：
Myers, Simon R.
中科院分区：
文献类型：
--
作者：
Altemose, Nicolas;Noor, Nudrat;Myers, Simon R.
PRDM9的结合定位了人类和小鼠几乎所有的减数分裂重组位点。然而，大多数prdm9结合的位点不会成为重组热点。为了探索影响结合和随后重组结果的因素，我们在转染的人类细胞系中绘制了人类PRDM9结合位点，并测量了PRDM9诱导的组蛋白修饰。这些数据揭示了PRDM9不同的dna结合方式。我们还发现人类PRDM9经常结合启动子，尽管它们的重组率很低，并且它可以激活包括CTCFL和VCX在内的少数基因的表达。此外，我们确定了特定的序列基序，这些基序预测了PRDM9结合位点周围一致的、局部的减数分裂重组抑制。这些基序与KRAB-ZNF蛋白结合、TRIM28募集和特异性组蛋白修饰密切相关。最后，我们证明，除了结合DNA外，PRDM9的锌指也介导其多聚体，并且我们表明一对高度分化的等位基因优先形成同源多聚体。
PRDM9 binding localizes almost all meiotic recombination sites in humans and mice. However, most PRDM9-bound loci do not become recombination hotspots. To explore factors that affect binding and subsequent recombination outcomes, we mapped human PRDM9 binding sites in a transfected human cell line and measured PRDM9-induced histone modifications. These data reveal varied DNA-binding modalities of PRDM9. We also find that human PRDM9 frequently binds promoters, despite their low recombination rates, and it can activate expression of a small number of genes including CTCFL and VCX. Furthermore, we identify specific sequence motifs that predict consistent, localized meiotic recombination suppression around a subset of PRDM9 binding sites. These motifs strongly associate with KRAB-ZNF protein binding, TRIM28 recruitment, and specific histone modifications. Finally, we demonstrate that, in addition to binding DNA, PRDM9's zinc fingers also mediate its multimerization, and we show that a pair of highly diverged alleles preferentially form homo-multimers.