The PRDM9 KRAB domain is required for meiosis and involved in protein interactions.

The PRDM9 KRAB domain is required for meiosis and involved in protein interactions.
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DOI:
10.1007/s00412-017-0631-z
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发表时间:
2017-12
期刊:
影响因子:
1.6
通讯作者:
de Massy B
de Massy B
中科院分区:
生物学3区
文献类型:
--
作者:
Imai Y;Baudat F;Taillepierre M;Stanzione M;Toth A;de Massy B

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PR结构域蛋白9(PRDM 9)是人类和小鼠基因组中减数分裂重组热点定位的主要调节因子。这种作用涉及其DNA结合结构域,其由锌指串联阵列组成,以及PRDM 9依赖的组蛋白H3在赖氨酸4处的三甲基化。PRDM 9是PRDM家族转录调节因子的一员,但与其他家族成员不同的是,它包含一个Krüppel相关框(KRAB)相关结构域,该结构域被预测为潜在的蛋白质相互作用结构域。在这里,我们表明,截短小鼠PRDM 9的KRAB结构域导致PRDM 9功能的丧失和减数分裂前期和配子发生的改变。此外,我们还鉴定了在酵母双杂交试验筛选中与PRDM 9的KRAB结构域相互作用的蛋白质,特别是COMPASS复合物的成员CXXC 1。我们还表明,CXXC 1与IHO 1,减数分裂双链断裂(DSB)机制的重要组成部分相互作用。由于CXXC 1是orthopathic的酿酒酵母Spp 1,连接DSB网站的DSB机器的染色体轴上,我们建议,这些分子间的相互作用参与调节减数分裂DSB形成是保守的小鼠减数分裂。本文的在线版本(doi:10.1007/s 00412 -017-0631-z)包含补充材料,可供授权用户使用。
PR domain-containing protein 9 (PRDM9) is a major regulator of the localization of meiotic recombination hotspots in the human and mouse genomes. This role involves its DNA-binding domain, which is composed of a tandem array of zinc fingers, and PRDM9-dependent trimethylation of histone H3 at lysine 4. PRDM9 is a member of the PRDM family of transcription regulators, but unlike other family members, it contains a Krüppel-associated box (KRAB)-related domain that is predicted to be a potential protein interaction domain. Here, we show that truncation of the KRAB domain of mouse PRDM9 leads to loss of PRDM9 function and altered meiotic prophase and gametogenesis. In addition, we identified proteins that interact with the KRAB domain of PRDM9 in yeast two-hybrid assay screens, particularly CXXC1, a member of the COMPASS complex. We also show that CXXC1 interacts with IHO1, an essential component of the meiotic double-strand break (DSB) machinery. As CXXC1 is orthologous to Saccharomyces cerevisiae Spp1 that links DSB sites to the DSB machinery on the chromosome axis, we propose that these molecular interactions involved in the regulation of meiotic DSB formation are conserved in mouse meiosis. The online version of this article (doi:10.1007/s00412-017-0631-z) contains supplementary material, which is available to authorized users.
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