Tetrahymena JMJD3 homolog regulates H3K27 methylation and nuclear differentiation

• Main Authors: Pei-Han Chung, 鍾沛翰
• Other Authors: Meng-Chao Yao
• Format: Others
• Language: en_US
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/25377245991530590935

博士 === 國防醫學院 === 生命科學研究所 === 100 === 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 a H3K27me3 demethylase might exist. Therefore, an interesting question to ask is what are the nuclear developmental processes controlled by this unknown H3K27me3 demethylase. In my PhD thesis, I report a novel 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, knocking down 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 EZL1 partially restored the 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.