During meiotic prophase, sister chromatids are organized into axial element (AE), which underlies the structural framework for the meiotic events such as meiotic recombination and homolog synapsis. HORMA domain-containing proteins (HORMADs) localize along AE and play critical roles in the regulation of those meiotic events. Organization of AE is attributed to two groups of proteins: meiotic cohesins REC8 and RAD21L; and AE components SYCP2 and SYCP3. It has been elusive how these chromosome structural proteins contribute to the chromatin loading of HORMADs prior to AE formation. Here we newly generated Sycp2 null mice and showed that initial chromatin loading of HORMAD1 was mediated by meiotic cohesins prior to AE formation. HORMAD1 interacted not only with the AE components SYCP2 and SYCP3 but also with meiotic cohesins. Notably, HORMAD1 interacted with meiotic cohesins even in Sycp2-KO, and localized along cohesin axial cores independently of the AE components SYCP2 and SYCP3. Hormad1/Rad21L-double knockout (dKO) showed more severe defects in the formation of synaptonemal complex (SC) compared to Hormad1-KO or Rad21L-KO. Intriguingly, Hormad1/Rec8-dKO but not Hormad1/Rad21L-dKO showed precocious separation of sister chromatid axis. These findings suggest that meiotic cohesins REC8 and RAD21L mediate chromatin loading and the mode of action of HORMAD1 for synapsis during early meiotic prophase.

在减数分裂前期，姐妹染色单体被组织成轴向元件（AE），这是减数分裂事件（例如减数分裂重组和同源突触）的结构框架的基础。含HORMA域的蛋白质（HORMAD）沿AE定位，并在调节这些减数分裂事件中起关键作用。AE的组织归因于两组蛋白质：减数分裂黏着蛋白REC8和RAD21L；和AE组件SYCP2和SYCP3。这些染色体结构蛋白如何在AE形成之前对HORMAD的染色质负载做出贡献一直是难以捉摸的。在这里，我们新生成了Sycp2结果显示，在AE形成之前，减数分裂粘附素介导了HORMAD1的初始染色质负载。HORMAD1不仅与AE组件SYCP2和SYCP3相互作用，而且还与减数分裂黏附素相互作用。值得注意的是，即使在Sycp2- KO中，HORMAD1也与减数分裂黏附素相互作用，并独立于AE组件SYCP2和SYCP3沿黏附素轴向核心定位。与Hormad1- KO或Rad21L- KO相比，Hormad1 / Rad21L-双敲除（dKO）在突触复合体（SC）的形成中显示出更严重的缺陷。有趣的是，Hormad1 / Rec8 -dKO但不是Hormad1 / Rad21L-dKO显示姐妹染色单体轴早熟分离。这些发现表明减数分裂粘附素REC8和RAD21L在减数分裂前期阶段介导染色质负载和HORMAD1对突触的作用方式。