Valls Ester, Sánchez-Molina Sara, Martínez-Balbás Marian A
Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Parc Cientific de Barcelona, Josep Samitier 1-5, 08028 Barcelona, Spain.
J Biol Chem. 2005 Dec 30;280(52):42592-600. doi: 10.1074/jbc.M507407200. Epub 2005 Sep 30.
The global inhibition of transcription at the mitotic phase of the cell cycle occurs together with the general displacement of transcription factors from the mitotic chromatin. Nevertheless, the DNase- and potassium permanganate-hypersensitive sites are maintained on potentially active promoters during mitosis, helping to mark active genes at this stage of the cell cycle. Our study focuses on the role of histone acetylation and H3 (Lys-4) methylation in the maintenance of the competency of these active genes during mitosis. To this end we have analyzed histone modifications across the promoters and coding regions of constitutively active, inducible, and inactive genes in mitotic arrested cells. Our results show that basal histone modifications are maintained during mitosis at promoters and coding regions of the active and inducible RNA polymerase II-transcribed genes. In addition we have demonstrated that, together with H3 acetylation and H3 (Lys-4) methylation, H4 (Lys-12) acetylation at the coding regions contributes to the formation of a stable mark on active genes at this stage of the cell cycle. Finally, analysis of cyclin B1 gene activation during mitosis revealed that the former occurs with a strong increase of H3 (Lys-4) trimethylation but not H3 or H4 acetylation, suggesting that histone methyltransferases are active during this stage. These data demonstrate a critical role of histone acetylation and H3 (Lys-4) methylation during mitosis in marking and activating genes during the mitotic stage of the cell cycle.
在细胞周期的有丝分裂期，转录的全局抑制与转录因子从有丝分裂染色质上的普遍位移同时发生。然而，在有丝分裂期间，脱氧核糖核酸酶和高锰酸钾超敏位点在潜在的活性启动子上得以维持，有助于在细胞周期的这一阶段标记活性基因。我们的研究聚焦于组蛋白乙酰化和H3（赖氨酸-4）甲基化在有丝分裂期间维持这些活性基因活性方面的作用。为此，我们分析了有丝分裂停滞细胞中组成型活性基因、可诱导基因和非活性基因的启动子及编码区域的组蛋白修饰情况。我们的结果表明，在有丝分裂期间，活性和可诱导的RNA聚合酶II转录基因的启动子及编码区域会维持基础组蛋白修饰。此外，我们还证明，在细胞周期的这一阶段，编码区域的H4（赖氨酸-12）乙酰化与H3乙酰化和H3（赖氨酸-4）甲基化一起，有助于在活性基因上形成稳定标记。最后，对有丝分裂期间细胞周期蛋白B1基因激活的分析表明，其激活伴随着H3（赖氨酸-4）三甲基化的强烈增加，而非H3或H4乙酰化的增加，这表明组蛋白甲基转移酶在这一阶段具有活性。这些数据证明了组蛋白乙酰化和H3（赖氨酸-4）甲基化在有丝分裂期间对细胞周期有丝分裂阶段的基因标记和激活起着关键作用。
