De Muyt Arnaud, Lee Sunkyung, Khanal Sushil, Toe Laurine Dal, Adam Céline, Mercier Raphael, Borde Valérie, Hunter Neil, Robert Thomas
Centre de Biologie Structurale (CBS), Univ Montpellier, CNRS, INSERM, 34090 Montpellier, France.
Howard Hughes Medical Institute, University of California Davis, Davis, CA 95616, USA.
bioRxiv. 2025 Aug 28:2025.08.25.672081. doi: 10.1101/2025.08.25.672081.
Meiotic crossovers are needed to produce genetically balanced gametes. In mammals, crossover formation is mediated by a conserved set of pro-crossover proteins via mechanisms that remain unclear. Here, we characterize a mammalian pro-crossover factor HEIP1. In mouse HEIP1 is essential for crossing over and fertility of both sexes. HEIP1 promotes crossing over by orchestrating the recruitment of other pro-crossover proteins, including the MutS complex (MSH4-MSH5) and E3 ligases (HEI10, RNF212, and RNF212B), that are required to mature crossover sites and recruit the crossover-specific resolution complex MutL. Moreover, HEIP1 directly interacts with HEI10, suggesting a direct role in controlling the recruitment of pro-crossover E3 ligases. During early stages of meiotic prophase I, HEIP1 interacts with the chromosome axes, independently of recombination, before relocalizing to the central region of the synaptonemal complex. We propose that HEIP1 is a new conserved master regulator of crossover proteins that controls different crossover maturation steps.
减数分裂交叉对于产生基因平衡的配子至关重要。在哺乳动物中，交叉形成由一组保守的促交叉蛋白通过尚不清楚的机制介导。在这里，我们对一种哺乳动物促交叉因子HEIP1进行了表征。在小鼠中，HEIP1对于两性的交叉和生育能力至关重要。HEIP1通过协调其他促交叉蛋白的募集来促进交叉，这些蛋白包括MutS复合物（MSH4 - MSH5）和E3连接酶（HEI10、RNF212和RNF212B），它们是成熟交叉位点并募集交叉特异性解离复合物MutL所必需的。此外，HEIP1直接与HEI10相互作用，表明其在控制促交叉E3连接酶的募集中起直接作用。在减数分裂前期I的早期阶段，HEIP1与染色体轴相互作用，独立于重组，然后重新定位到联会复合体的中央区域。我们提出HEIP1是一种新的保守的交叉蛋白主调节因子，可控制不同的交叉成熟步骤。
