Tetrahymena thermophila JMJD3 Homolog Regulates H3K27 Methylation and Nuclear Differentiation
Tetrahymena thermophila JMJD3 Homolog Regulates H3K27 Methylation and Nuclear Differentiation
复制标题
DOI：
10.1128/ec.05290-11
复制
发表时间：
2012-05-01
期刊：
影响因子：
--
通讯作者：
Yao, Meng-Chao
中科院分区：
文献类型：
--
作者：
Chung, Pei-Han;Yao, Meng-Chao
组蛋白H3K27me3修饰是发育和基因表达的重要调节因子。在嗜热四膜虫中，H3K27me3标记在核发育过程中的复杂染色质动力学表明可能存在H3K27me3去甲基酶。在此，我们报道了四膜虫中的一个H3K27me3去甲基酶同源物JMJ1。在接合过程中，JMJ1的表达上调，该蛋白首先定位于亲本大核，然后定位于新的大核。在接合细胞中，JMJ1的表达下调导致后代产量严重减少，这表明JMJ1是四膜虫接合所必需的。此外，JMJ1基因敲除导致新大核中H3K27三甲基化增加，DNA消除相关基因转录减少，DNA消除过程也被部分阻断。敲除H3K27甲基转移酶EZL2，而不是EZL1，部分恢复了JMJ1敲除细胞的后代产量，并减少了H3K27me3在新的大核中的异常积聚。综上所述，这些结果证明了JMJ1在调节H3K27me3接合过程中的关键作用，以及JMJ1在调节新的大核中的基因表达方面的重要性，但不是调节与程序性DNA缺失相关的异染色质的形成。
Histone H3K27me3 modification is an important regulator for development and gene expression. In Tetrahymena thermophila, the complex chromatin dynamics of H3K27me3 marks during nuclear development suggested that an H3K27me3 demethylase might exist. Here, we report an H3K27me3 demethylase homolog, JMJ1, in Tetrahymena. During conjugation, JMJ1 expression is upregulated and the protein is localized first in the parental macronucleus and then in the new macronucleus. In conjugating cells, knockdown of JMJ1 expression resulted in a severe reduction in the production of progeny, suggesting that JMJ1 is essential for Tetrahymena conjugation. Furthermore, knockdown of JMJ1 resulted in increased H3K27 trimethylation in the new macronucleus and reduced transcription of genes related to DNA elimination, while the DNA elimination process was also partially blocked. Knockdown of the H3K27 methyltransferase EZL2 but not that of EZL1 partially restored progeny production in JMJ1-knockdown cells and reduced abnormal H3K27me3 accumulation in the new macronucleus. Taken together, these results demonstrate a critical role for JMJ1 in regulating H3K27me3 during conjugation and the importance of JMJ1 in regulating gene expression in the new macronucleus but not in regulating the formation of heterochromatin associated with programmed DNA deletion.