DNA polymerase epsilon binds histone H3.1-H4 and recruits MORC1 to mediate meiotic heterochromatin condensation.
DNA polymerase epsilon binds histone H3.1-H4 and recruits MORC1 to mediate meiotic heterochromatin condensation.
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DOI：
10.1073/pnas.2213540119
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发表时间：
2022-10-25
影响因子：
11.1
通讯作者：
Wang, Yingxiang
中科院分区：
文献类型：
--
作者：
Wang, Cong;Huang, Jiyue;Li, Yingping;Zhang, Jun;He, Chengpeng;Li, Tianyang;Jiang, Danhua;Dong, Aiwu;Ma, Hong;Copenhaver, Gregory P.;Wang, Yingxiang
减数分裂前期 I 期间异染色质浓缩促进同源染色体相互作用并确保其准确分离，从而保持基因组完整性。然而，人们对减数分裂异染色质浓缩的调控机制知之甚少，尤其是在植物中。在这里，我们证明DNA聚合酶ε的拟南芥催化亚基（POL2A）是减数分裂异染色质形成所必需的。 POL2A 中的两个不同结构域促进异染色质浓缩，一个是与异染色质富集的组蛋白变体 H3.1-H4 结合的 C 端锌指结构域 (ZF1)，另一个是招募 GHKL 三磷酸腺苷酶 (ATPase) MORC1 的 N 端。我们还证明小鼠 POL2A ZF1 与 H3.1-H4 结合，表明此处确定的机制似乎是保守的。这些结果将 POL ε 的作用扩展到 DNA 复制之外。异染色质对于真核生物基因组的完整性和稳定性至关重要。调节减数分裂异染色质形成的机制在很大程度上仍不清楚。在这里，我们证明拟南芥 DNA 聚合酶 epsilon (POL ε) 的催化亚基 (POL2A) 对于减数分裂异染色质的正确形成是必需的。 POL2A N 末端与 GHKL 三磷酸腺苷酶 (ATPase) MORC1 (Microrchidia 1) 相互作用，并且 POL2A 是 MORC1 在减数分裂异染色质上的定位所必需的。影响 POL2A N 末端的突变会导致减数分裂异染色质形态异常，这也在 morc1 中观察到。此外，POL2A C 端锌指结构域 (ZF1) 特异性结合组蛋白 H3.1-H4 二聚体或四聚体，对于减数分裂异染色质凝聚非常重要。有趣的是，我们还发现小鼠对应物具有类似的 H3.1 结合特异性。总之，我们的结果表明，POL2A、ZF1 和 N 末端的两个不同结构域分别结合 H3.1-H4 并招募 MORC1，以诱导减数分裂异染色质组织的连续过程。这些活动扩展了 POL ε 的功能范围，超越了其在 DNA 复制中的经典作用，并且似乎在动物和植物中是保守的。
Heterochromatin condensation during meiotic prophase I facilitates homologous chromosome interactions and ensures their accurate segregation, thereby maintaining genome integrity. However, the regulatory mechanisms governing meiotic heterochromatin condensation are poorly understood, especially in plants. Here, we show that the Arabidopsis catalytic subunit (POL2A) of DNA polymerase epsilon is required for meiotic heterochromatin formation. Two distinct domains in POL2A promote heterochromatin condensation, a C-terminal zinc finger domain (ZF1) that binds to the heterochromatin-enriched histone variant H3.1-H4 and the N terminus, which recruits the GHKL adenosine triphosphatase (ATPase) MORC1. We also demonstrate that mouse POL2A ZF1 binds to H3.1-H4, suggesting that the mechanism identified here appears to be conserved. These results expand the role of POL ε beyond DNA replication. Heterochromatin is essential for genomic integrity and stability in eukaryotes. The mechanisms that regulate meiotic heterochromatin formation remain largely undefined. Here, we show that the catalytic subunit (POL2A) of Arabidopsis DNA polymerase epsilon (POL ε) is required for proper formation of meiotic heterochromatin. The POL2A N terminus interacts with the GHKL adenosine triphosphatase (ATPase) MORC1 (Microrchidia 1), and POL2A is required for MORC1’s localization on meiotic heterochromatin. Mutations affecting the POL2A N terminus cause aberrant morphology of meiotic heterochromatin, which is also observed in morc1. Moreover, the POL2A C-terminal zinc finger domain (ZF1) specifically binds to histone H3.1-H4 dimer or tetramer and is important for meiotic heterochromatin condensation. Interestingly, we also found similar H3.1-binding specificity for the mouse counterpart. Together, our results show that two distinct domains of POL2A, ZF1 and N terminus bind H3.1-H4 and recruit MORC1, respectively, to induce a continuous process of meiotic heterochromatin organization. These activities expand the functional repertoire of POL ε beyond its classic role in DNA replication and appear to be conserved in animals and plants.
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影响因子：
4.5
作者：
Da Ines O;Abe K;Goubely C;Gallego ME;White CI
通讯作者：
White CI
DOI：
10.1038/nrm4043
发表时间：
2015-09
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Du J;Johnson LM;Jacobsen SE;Patel DJ
通讯作者：
Patel DJ
影响因子：
9.4
作者：
Benoit, Matthias;Simon, Lauriane;Probst, Aline V.
通讯作者：
Probst, Aline V.
影响因子：
3.5
作者：
Inoue, N;Hess, KD;Zinn, AR
通讯作者：
Zinn, AR
影响因子：
11.4
作者：
Hoppmann, Verena;Thorstensen, Tage;Aasland, Rein
通讯作者：
Aasland, Rein