히스톤 탈메틸화 효소에 의한 전사 조절 기전 연구

Abstract

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 and lysine 79 is linked to telomeric silencing, the roles of histone demethylases in transcription and silencing regulation are not understood. Here we show all histone H3 methylation pattern of actively transcribed genes and telomeric region in wild-type and JmjC protein deletion mutants of S. cerevisiae by systematically analyzed site-specific chromatin immunoprecipitation. Crosslinking pattern of the H3K36me3 matched that of RNApII, while H3K4me was enriched at promoter-proximal region and H3K79me was found throughout the transcribed genes. And our results indicate that RPH1 functions as a specific demethylase for H3 K36me3, directly regulating lysine 36 methylation in transcribed regions. Histone H3 lysine 79 trimethylation is decreased within the body of actively transcribed gene and telomere proximal site in each JmjC protein deletion mutants. Interestingly, loss of each JmjC protein increased H3K36me2,3 but decreased H3K79me3 at the telomere proximal site. We show that all JmjC proteins enhance the position effect variegation. Thus, we suggest that JmjC proteins modulate gene silencing through differential regulation of demethylation at H3K36 and H3K79.