Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.
Department of Biochemistry, National University of Singapore, Singapore.
J Cell Biol. 2019 Sep 2;218(9):2896-2918. doi: 10.1083/jcb.201903125. Epub 2019 Jul 26.
Meiosis generates four genetically distinct haploid gametes over the course of two reductional cell divisions. Meiotic divisions are characterized by the coordinated deposition and removal of various epigenetic marks. Here we propose that nuclear respiratory factor 1 (NRF1) regulates transcription of euchromatic histone methyltransferase 1 (EHMT1) to ensure normal patterns of H3K9 methylation during meiotic prophase I. We demonstrate that cyclin-dependent kinase (CDK2) can bind to the promoters of a number of genes in male germ cells including that of through interaction with the NRF1 transcription factor. Our data indicate that CDK2-mediated phosphorylation of NRF1 can occur at two distinct serine residues and negatively regulates NRF1 DNA binding activity in vitro. Furthermore, induced deletion of in spermatocytes results in increased expression of many NRF1 target genes including We hypothesize that the regulation of NRF1 transcriptional activity by CDK2 may allow the modulation of expression, therefore controlling the dynamic methylation of H3K9 during meiotic prophase.
减数分裂在两次减数分裂过程中产生四个遗传上不同的单倍体配子。减数分裂的特征是各种表观遗传标记的协调沉积和去除。在这里，我们提出核呼吸因子 1（NRF1）调节常染色质组蛋白甲基转移酶 1（EHMT1）的转录，以确保减数分裂前期 I 期间 H3K9 甲基化的正常模式。我们证明细胞周期蛋白依赖性激酶 2（CDK2）可以通过与 NRF1 转录因子的相互作用，与雄性生殖细胞中许多基因（包括）的启动子结合。我们的数据表明，CDK2 介导的 NRF1 的磷酸化可以在两个不同的丝氨酸残基上发生，并在体外负调节 NRF1 的 DNA 结合活性。此外，诱导敲除减数分裂精母细胞中的导致许多 NRF1 靶基因的表达增加，包括 我们假设 CDK2 对 NRF1 转录活性的调节可能允许 表达的调节，从而控制减数分裂前期 H3K9 的动态甲基化。
