Set3 HDAC Mediates Effects of Overlapping Noncoding Transcription on Gene Induction Kinetics

Abstract

Set3 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 non-coding RNA (ncRNA) transcription. Many Set3-repressed genes have H3K4me2 instead of me3 over promoter regions, due either to reduced H3K4me3 or ncRNA transcription from distal or anti-sense promoters. The resulting deacetylation by Set3C slows gene induction. Set3C 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 anti-sense transcript. These results suggest that Set3C and overlapping non-coding transcription can cooperate to fine tune the response kinetics of individual genes.

Native elongating transcript sequencing reveals global anti-correlation between sense and antisense nascent transcription in fission yeast

“…Importantly, XUTs can accumulate in wild-type (WT) cells under physiological stress, modulating the RNA decay activity (Van Dijk et al 2011), and other antisense transcripts were shown to respond to cell differentiation programs such as meiosis (Lardenois et al 2011). This indicates that RNA surveillance pathways can indeed be considered as regulatory switches of gene expression, probably combined to histone modifications (Camblong et al 2007;Houseley et al 2008;Pinskaya et al 2009;Van Dijk et al 2011;Kim et al 2012).…”

Setd5 is essential for mammalian development and the co-transcriptional regulation of histone acetylation

“…Given that SETD5 orthologs have been shown to be involved in cotranscriptional chromatin deacetylation, a process that increases the productive transcription of active genes by suppressing off-target transcription (Kim et al, 2012;Rincon-Arano et al, 2012), we sought to determine whether SETD5 has a similar function. We analyzed the chromatin acetylation status of three constitutively expressed genes using anti-acetylated histone chromatin immunoprecipitation (ChIP) followed by PCR with primers targeting different regions within and downstream of the promoter region (Fig.…”

“…The genes selected for this analysis were eukaryotic translation elongation factor 1 alpha 1 (Eef1a1), hydroxyacyl glutathione hydrolase (Hagh) and inositol hexaphosphate kinase 1 (Ip6k1). Eef1a1 is a housekeeping gene, whereas Hagh and Ip6k1 are two metabolic genes that have antisense transcripts near or within the gene locus and whose yeast orthologs were analyzed in studies of Set3p (Kim et al, 2012). ChIP experiments were performed using chromatin isolated from Setd5 GFP/+ and Setd5 GFP/GFP mESC lines, as well as Setd5 GFP/GFP cells in which Setd5 expression was rescued through overexpression of FLAG-SETD5 protein under the control of the human EEF1A1 promoter.…”

LncRNAs: Bridging environmental sensing and gene expression

“…103 Repression URA2 Pyrimidine biogenesis YES usDCI1. 104 Repression DCI1 Fatty acid metabolism YES GAL10 lncRNA 47,48,105 Repression GAL genes Galactose metabolism YES GAL10/GAL10s lncRNAs. 52,53 Promotes induction GAL genes Galactose metabolism YES KCS1 lncRNAs 106 Translational interference KCS1 Inositol hexa/hepta bisphosphate kinase YES SUT719 30,35 Repression SUR7 Plasma membrane protein YES CDC28 AS RNA 29 Promotes induction CDC28 Cell cycle regulator NO RTL.…”