Kim Taesoo, Buratowski Stephen
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Biol Chem. 2007 Jul 20;282(29):20827-35. doi: 10.1074/jbc.M703034200. Epub 2007 May 24.
Histone methylation is a reversible modification regulated by the antagonistic functions of residue-specific histone methyltransferases and demethylases. Although methylation of histone H3 at lysines 4 and 36 is linked to transcription, the roles of histone demethylases in transcription regulation are not understood. Here we show that overexpression of either Jhd1 or Rph1, two JmjC-domain proteins, bypasses the requirement for the positive elongation factor gene BUR1. Biochemical analysis and chromatin immunoprecipitation experiments indicate that Rph1 functions as a specific demethylase for H3 K36me3 and K36me2, directly regulating Lys(36) methylation in transcribed regions. Both Jhd1 and Rph1 are required for normal levels of RNA polymerase II cross-linking to genes. Taken together, these findings indicate that a general function of histone demethylases for H3 Lys(36) is to promote transcription elongation by antagonizing repressive Lys(36) methylation by Set2.
组蛋白甲基化是一种可逆修饰，由残基特异性组蛋白甲基转移酶和去甲基化酶的拮抗作用调控。尽管组蛋白H3赖氨酸4和36位的甲基化与转录相关，但组蛋白去甲基化酶在转录调控中的作用尚不清楚。在此我们表明，两种含JmjC结构域的蛋白Jhd1或Rph1的过表达可绕过对正向延伸因子基因BUR1的需求。生化分析和染色质免疫沉淀实验表明，Rph1作为H3 K36me3和K36me2的特异性去甲基化酶，直接调控转录区域中赖氨酸36的甲基化。Jhd1和Rph1都是RNA聚合酶II与基因交联达到正常水平所必需的。综上所述，这些发现表明，组蛋白去甲基化酶对H3赖氨酸36的一般功能是通过拮抗Set2介导的抑制性赖氨酸36甲基化来促进转录延伸。
