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Roles for Ctk1 and Spt6 in Regulating the Different Methylation States of Histone H3 Lysine 36

机译:Ctk1和Spt6在调节组蛋白H3赖氨酸的不同甲基化状态中的作用36

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Set2 (KMT3)-dependent methylation (me) of histone H3 at lysine 36 (H3K36) promotes deacetylation of transcribed chromatin and represses cryptic promoters within genes. Although Set2 is the only methyltransferase (KMTase) for H3K36 in yeast, it is not known if Set2 is regulated or whether the different methylation states at H3K36 are functionally distinct. Here we show that the N-terminal 261 residues of Set2 (Set21-261), containing the SET KMTase domain, are sufficient for H3K36me2, histone deacetylation, and repression of cryptic promoters at STE11. Set2-catalyzed H3K36me2 does not require either Ctk1-dependent phosphorylation of RNA polymerase II (RNAPII) or the presence of the phospho-C-terminal domain (CTD) interaction (SRI) domain of Set2. This finding is consistent with a known correlation between H3K36me2 and whether a gene is on or off, but not the level of activity of a gene. By contrast, H3K36me3 requires Spt6, proline 38 on histone H3 (H3P38), the CTD of RNAPII, Ctk1, and the C-terminal SRI domain of Set2. We suggest that the C-terminal region of Set2, in conjunction with the phosphorylated CTD of RNAPII, influences the KMTase activity to promote H3K36me3 during transcription elongation.
机译:赖氨酸36(H3K36)上组蛋白H3的Set2(KMT3)依赖性甲基化(me)促进转录的染色质脱乙酰化并抑制基因内的隐秘启动子。尽管Set2是酵母中H3K36的唯一甲基转移酶(KMTase),但尚不清楚Set2是否受调控或H3K36的不同甲基化状态在功能上是否不同。在这里,我们显示了包含SET KMTase域的Set2(Set2 1-261 )的N端261个残基足以用于H3K36me2,组蛋白脱乙酰化和抑制 STE11处的启动子。 Set2催化的H3K36me2不需要RNA聚合酶II(RNAPII)的Ctk1依赖性磷酸化或Set2的磷酸C末端结构域(CTD)相互作用(SRI)结构域的存在。这一发现与H3K36me2与基因是否开启或关闭之间的已知相关性一致,但与基因活性水平不相关。相比之下,H3K36me3需要组蛋白H3(H3P38)上的Spt6,脯氨酸38,RNAPII的CTD,Ctk1和Set2的C端SRI结构域。我们建议,Set2的C末端区域与RNAPII的磷酸化CTD结合,影响KMTase活性以在转录延伸过程中促进H3K36me3。

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