Epigenetic Regulation of TET1-SP1 During Spermatogonia Self-Renewal and Proliferation.
Epigenetic Regulation of TET1-SP1 During Spermatogonia Self-Renewal and Proliferation.
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TET1-SP1在精原细胞自我更新和增殖过程中的表观遗传调控
DOI：
10.3389/fphys.2022.843825
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发表时间：
2022
影响因子：
4
通讯作者：
Zheng L
中科院分区：
文献类型：
--
作者：
Liu L;Wang J;Wang S;Wang M;Chen Y;Zheng L
精原细胞是生精波的来源。精原细胞异常可引起异常的生精波，表现为少精子、少精子、无精子等生精障碍。其中，精原细胞的自我更新是维持精子发生过程的基础，精原细胞自我更新与分化之间的密切调节平衡可以维持精子的持续产生。泰特甲基胞嘧啶双加氧酶1（TET 1）是一种重要的表位修饰酶，催化5-甲基胞嘧啶（5-mC）转化为5-羟甲基胞嘧啶（5-hmC），从而引起特定基因位点的甲基化羟基化，实现DNA去甲基化过程，调控基因表达。然而，TET 1特异性作用的羟甲基化位点和影响关键差异基因的相互作用机制尚不清楚。在本研究中，我们提供的证据表明，PLZF的表达，精原细胞自我更新的标记基因，TET 1过表达组显着升高，而PCNA的表达，增殖相关的标记基因，也在mRNA水平上升高。测序结果显示SP1的表达有显著差异。TET 1过表达后，SP1在mRNA和蛋白水平的表达均增加，差异表达基因DAXX在蛋白水平的表达下调，其对应蛋白P53的表达上调。综上所述，我们的研究结果提示TET 1过表达引起SP1、DAXX等基因表达的变化，SP1和DAXX之间存在一定的拮抗作用，最终达到动态平衡，维持精原细胞自我更新状态，以持续产生精子。这些发现可能有助于了解男性生殖系统疾病。
Spermatogonia are the source of spermatogenic waves. Abnormal spermatogonia can cause ab-normal spermatogenic waves, which manifest as spermatogenic disorders such as oligospermia, hypospermia, and azoospermia. Among them, the self-renewal of spermatogonia serves as the basis for maintaining the process of spermatogenesis, and the closely regulated balance between self-renewal and differentiation of spermatogonia can maintain the continuous production of spermatozoa. Tet methylcytosine dioxygenase 1(TET1) is an important epitope modifying enzyme that catalyzes the conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), thereby causing the methylation of specific genes site hydroxylation, enabling the DNA de-methylation process, and regulating gene expression. However, the hydroxymethylation sites at which TET1 acts specifically and the mechanisms of interaction affecting key differential genes are not clear. In the present study, we provide evidence that the expression of PLZF, a marker gene for spermatogonia self-renewal, was significantly elevated in the TET1 overexpression group, while the expression of PCNA, a proliferation-related marker gene, was also elevated at the mRNA level. Significant differential expression of SP1 was found by sequencing. SP1 expression was increased at both mRNA level and protein level after TET1 overexpression, while differential gene DAXX expression was downregulated at protein level, while the expression of its reciprocal protein P53 was upregulated. In conclusion, our results suggest that TET1 overexpression causes changes in the expression of SP1, DAXX and other genes, and that there is a certain antagonistic effect between SP1 and DAXX, which eventually reaches a dynamic balance to maintain the self-renewal state of spermatogonia for sustained sperm production. These findings may contribute to the understanding of male reproductive system disorders.
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影响因子：
12.4
作者：
通讯作者：
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影响因子：
30.5
作者：
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影响因子：
4.8
作者：
Liu, Yingdong;Zhang, Yanping;Liu, Wenqiang
通讯作者：
Liu, Wenqiang
影响因子：
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作者：
Nye J;Melters DP;Dalal Y
通讯作者：
Dalal Y
影响因子：
3.1
作者：
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通讯作者：
Ryoo ZY