Modulation of gene expression dynamics by co-Transcriptional histone methylations

Hyeonju Woo, So Dam Ha, Sung Bae Lee, Stephen Buratowski, Tae Soo Kim

Research output: Contribution to journalReview articlepeer-review

48 Scopus citations

Abstract

Co-Transcriptional methylations of histone H3 at lysines 4 and 36, highly conserved methyl marks from yeast to humans, have profound roles in regulation of histone acetylation. These modifications function to recruit and/or activate distinct histone acetyltransferases (HATs) or histone deacetylases (HDACs). Whereas H3K4me3 increases acetylation at promoters via multiple HATs, H3K4me2 targets Set3 HDAC to deacetylate histones in 5′ transcribed regions. In 3′ regions of genes, H3K36me2/3 facilitates deacetylation by Rpd3S HDAC and slows elongation. Despite their important functions in deacetylation, no strong effects on global gene expression have been seen under optimized or laboratory growth conditions. Instead, H3K4me2-Set3 HDAC and Set2-Rpd3S pathways primarily delay the kinetics of messenger RNA (mRNA) and long noncoding RNA (lncRNA) induction upon environmental changes. A majority of mRNA genes regulated by these pathways have an overlapping lncRNA transcription either from an upstream or an antisense promoter. Surprisingly, the distance between mRNA and lncRNA promoters seems to specify the repressive effects of the two pathways. Given that co-Transcriptional methylations and acetylation have been linked to many cancers, studying their functions in a dynamic condition or during cancer progression will be much more important and help identify novel genes associated with cancers.

Original languageEnglish
Article number49
JournalExperimental and Molecular Medicine
Volume49
Issue number4
DOIs
StatePublished - 7 Apr 2017

Bibliographical note

Funding Information:
This research was supported by grants to TK (the Basic Science Research Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2013R1A1A1008634 and NRF-2012R1A5A1048236), the National Research Foundation of Korea funded by Korean Government (NRF-2013S1A2A2035342)).

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