The MUT9p kinase phosphorylates histone H3 threonine 3 and is necessary for heritable epigenetic silencing in Chlamydomonas
The MUT9p kinase phosphorylates histone H3 threonine 3 and is necessary for heritable epigenetic silencing in Chlamydomonas
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DOI：
10.1073/pnas.0711310105
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发表时间：
2008-04-29
影响因子：
11.1
通讯作者：
Cerutti, Heriberto
中科院分区：
文献类型：
--
作者：
Casas-Mollano, J. Armando;Jeong, Byeong-Ryool;Cerutti, Heriberto
染色质组织的变化正在成为真核生物DNA模板代谢几乎每个方面的关键调节因子。历史经历了许多，在很大程度上是可逆的，翻译后修饰，影响染色质结构。一些修饰，如组蛋白H3在赖氨酸4上的三甲基化（H3 K4 me 3），与转录激活相关，而其他修饰，如组蛋白H3在赖氨酸27上的甲基化（H3 K27 me），与沉默染色质相关。翻译后组蛋白修饰也可能参与染色质状态的遗传。组蛋白磷酸化与多种细胞过程有关，但由于这种修饰的动态性质，其在长期基因沉默中的潜在作用仍然相对未被探索。我们在这里报告说，衣原体突变体缺陷的丝氨酸/苏氨酸蛋白激酶（MUT 9 p），磷酸化的历史H3和H2 A，表现出缺陷的遗传抑制的转基因和转座子。此外，基于染色质免疫沉淀分析，磷酸化H3 T3（H3 T3 ph）和单甲基化H3 K4（H3 K4 me 1）与二/三甲基化H3 K4呈负相关，并优先与沉默的转录单位相关。相反，突变株中这些标记的丢失与转基因和转座子的转录再激活相关。我们的研究结果表明，H3 T3 ph和H3 K4 me 1作为加强表观遗传标记的功能，在衣原体常染色质基因座的沉默。
Changes in chromatin organization are emerging as key regulators in nearly every aspect of DNA-templated metabolism in eukaryotes. Histories undergo many, largely reversible, posttranslational modifications that affect chromatin structure. Some modifications, such as trimethylation of histone H3 on Lys 4 (H3K4me3), correlate with transcriptional activation, whereas others, such as methylation of histone H3 on Lys 27 (H3K27me), are associated with silent chromatin. Posttranslational histone modifications may also be involved in the inheritance of chromatin states. Histone phosphorylation has been implicated in a variety of cellular processes but, because of the dynamic nature of this modification, its potential role in long-term gene silencing has remained relatively unexplored. We report here that a Chlamydomonas reinhardtii mutant defective in a Ser/Thr protein kinase (MUT9p), which phosphorylates histories H3 and H2A, shows deficiencies in the heritable repression of transgenes and transposons. Moreover, based on chromatin immunoprecipitation analyses, phosphorylated H3T3 (H3T3ph) and monomethylated H3K4 (H3K4me1) are inversely correlated with di/trimethylated H3K4 and associate preferentially with silenced transcription units. Conversely, the loss of those marks in mutant strains correlates with the transcriptional reactivation of transgenes and transposons. Our results suggest that H3T3ph and H3K4me1 function as reinforcing epigenetic marks for the silencing of euchromatic loci in Chlamydomonas.