Set3 HDAC mediates effects of overlapping noncoding transcription on gene induction kinetics

Taesoo Kim, Zhenyu Xu, Sandra Clauder-Münster, Lars M. Steinmetz, Stephen Buratowski

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154 Scopus citations


The Set3 histone deacetylase complex (Set3C) binds histone H3 dimethylated at lysine 4 (H3K4me2) to mediate deacetylation of histones in 5′-transcribed regions. To discern how Set3C affects gene expression, genome-wide transcription was analyzed in yeast undergoing a series of carbon source shifts. Deleting SET3 primarily caused changes during transition periods, as genes were induced or repressed. Surprisingly, a majority of Set3-affected genes are overlapped by noncoding RNA (ncRNA) transcription. Many Set3-repressed genes have H3K4me2 instead of me3 over promoter regions, due to either reduced H3K4me3 or ncRNA transcription from distal or antisense promoters. Set3C also represses internal cryptic promoters, but in different regions of genes than the Set2/Rpd3S pathway. Finally, Set3C stimulates some genes by repressing an overlapping antagonistic antisense transcript. These results show that overlapping noncoding transcription can fine-tune gene expression, not via the ncRNA but by depositing H3K4me2 to recruit the Set3C deacetylase.

Original languageEnglish
Pages (from-to)1158-1169
Number of pages12
Issue number6
StatePublished - 14 Sep 2012

Bibliographical note

Funding Information:
We are grateful to Angelika Amon (MIT) for sharing unpublished work, Sebastian Marquardt for the northern blot analysis protocol, and Ollie Rando (University of Massachusetts, Worcester) and all members of the Buratowski lab for helpful advice and discussions. T.K. is a Special Fellow of the Leukemia and Lymphoma Society. This research was supported by grants GM068717 to L.M.S. and GM46498 and GM56663 to S.B. from the US National Institutes of Health.


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