Iyer-Bierhoff Aishwarya, Grummt Ingrid
German Cancer Research Centre, DKFZ-ZMBH Alliance, Heidelberg, Germany.
Epigenet Insights. 2019 May 21;12:2516865719849090. doi: 10.1177/2516865719849090. eCollection 2019.
Entry into mitosis correlates with nucleolar disassembly and shutdown of ribosomal RNA (rRNA) gene (rDNA) transcription. In telophase, nucleoli reform and transcription is reactivated. The molecular mechanisms underlying the dynamics of nucleolar transcription during the cell cycle are manifold. Although mitotic inactivation of the RNA polymerase I (Pol I) transcription machinery by posttranslational modifications has been extensively studied, little is known about the structure of rDNA chromatin during progression through mitosis. Methylation of histone H2A at glutamine 104 (H2AQ104me), a dedicated nucleolar histone modification, is lost in prometaphase, leading to chromatin compaction, which enforces mitotic repression of rRNA genes. At telophase, restoration of H2AQ104me is required for the activation of transcription. H2AQ104 methylation and chromatin dynamics are regulated by fibrillarin (FBL) and the NAD-dependent nucleolar deacetylase sirtuin 7 (SIRT7). Deacetylation of FBL is required for the methylation of H2AQ104 and high levels of rDNA transcription during interphase. At the entry into mitosis, nucleoli disassemble and FBL is hyperacetylated, leading to loss of H2AQ104me, chromatin compaction, and shutdown of Pol I transcription. These results reveal that reversible acetylation of FBL regulates methylation of nucleolar H2AQ104, thereby reinforcing oscillation of Pol I transcription during the cell cycle.
进入有丝分裂与核仁解体以及核糖体RNA（rRNA）基因（rDNA）转录的停止相关。在末期，核仁重新形成且转录重新激活。细胞周期中核仁转录动态变化的分子机制是多方面的。尽管RNA聚合酶I（Pol I）转录机制通过翻译后修饰的有丝分裂失活已得到广泛研究，但对于有丝分裂过程中rDNA染色质的结构却知之甚少。组蛋白H2A在谷氨酰胺104位点（H2AQ104me）的甲基化是一种专门的核仁组蛋白修饰，在前期消失，导致染色质压缩，从而加强rRNA基因的有丝分裂抑制。在末期，H2AQ104me的恢复是转录激活所必需的。H2AQ104甲基化和染色质动态变化受纤维蛋白原（FBL）和NAD依赖性核仁脱乙酰酶沉默调节蛋白7（SIRT7）调控。FBL的去乙酰化是间期H2AQ104甲基化和高水平rDNA转录所必需的。进入有丝分裂时，核仁解体且FBL高度乙酰化，导致H2AQ104me丢失、染色质压缩以及Pol I转录停止。这些结果表明FBL的可逆乙酰化调节核仁H2AQ104的甲基化，从而加强细胞周期中Pol I转录的振荡。
