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Modulation of gene expression dynamics by co-transcriptional histone methylations
우현주,하소담,이성배,Stephen Buratowski,김태수 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-
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.
Phosphorylation of the yeast Rpb1 C-terminal domain at serines 2, 5, and 7.
Kim, Minkyu,Suh, Hyunsuk,Cho, Eun-Jung,Buratowski, Stephen American Society for Biochemistry and Molecular Bi 2009 The Journal of biological chemistry Vol.284 No.39
<P>The C-terminal domain (CTD) of Rpb1, the largest subunit of RNA polymerase II, acts as a binding platform for various mRNA processing and histone-modifying enzymes that act co-transcriptionally. These factors are targeted to specific phosphorylation states of the CTD that predominate at different stages of transcription. Within the repeating sequence YSPTSPS, serines 2 and 5 are major phosphorylation sites, but serine 7 phosphorylation was recently discovered in mammalian cells. Here we show that CTD serine 7 is also phosphorylated in yeast and that Ser-7(P) chromatin immunoprecipitation patterns resemble those of Ser-5(P). The basal factor TFIIH can phosphorylate Ser-7 in vitro and is necessary for Ser-7(P) in vivo. Interestingly, deletion of the CTD Ser-5(P) phosphatase Rtr1 leads to an increase in Ser-5(P) but not Ser-7(P).</P>
Proteomic Analysis Demonstrates Activator- and Chromatin-specific Recruitment to Promoters
Sikorski, Timothy W.,Joo, Yoo Jin,Ficarro, Scott B.,Askenazi, Manor,Buratowski, Stephen,Marto, Jarrod A. American Society for Biochemistry and Molecular Bi 2012 The Journal of biological chemistry Vol.287 No.42
<P>In-depth characterization of RNA polymerase II preinitiation complexes remains an important and challenging goal. We used quantitative mass spectrometry to explore context-dependent <I>Saccharomyces cerevisiae</I> preinitiation complex formation at the <I>HIS4</I> promoter reconstituted on naked and chromatinized DNA templates. The transcription activators Gal4-VP16 and Gal4-Gcn4 recruited a limited set of chromatin-related coactivator complexes, namely the chromatin remodeler Swi/Snf and histone acetyltransferases SAGA and NuA4, suggesting that transcription stimulation is mediated through these factors. Moreover, the two activators differentially recruited the coactivator complexes, consistent with specific activator-coactivator interactions. Chromatinized templates suppressed recruitment of basal transcription factors, thereby amplifying the effect of activators, compared with naked DNA templates. This system is sensitive, highly reproducible, and easily applicable to mapping the repertoire of proteins found at any promoter.</P>
Determinants of Histone H3K4 Methylation Patterns
Soares, Luis M.,He, P. Cody,Chun, Yujin,Suh, Hyunsuk,Kim, TaeSoo,Buratowski, Stephen Cell Press 2017 Molecular cell Vol.68 No.4
<P><B>Summary</B></P> <P>Various factors differentially recognize trimethylated histone H3 lysine 4 (H3K4me3) near promoters, H3K4me2 just downstream, and promoter-distal H3K4me1 to modulate gene expression. This methylation “gradient” is thought to result from preferential binding of the H3K4 methyltransferase Set1/complex associated with Set1 (COMPASS) to promoter-proximal RNA polymerase II. However, other studies have suggested that location-specific cues allosterically activate Set1. Chromatin immunoprecipitation sequencing (ChIP-seq) experiments show that H3K4 methylation patterns on active genes are not universal or fixed and change in response to both transcription elongation rate and frequency as well as reduced COMPASS activity. Fusing Set1 to RNA polymerase II results in H3K4me2 throughout transcribed regions and similarly extended H3K4me3 on highly transcribed genes. Tethered Set1 still requires histone H2B ubiquitylation for activity. These results show that higher-level methylations reflect not only Set1/COMPASS recruitment but also multiple rounds of transcription. This model provides a simple explanation for non-canonical methylation patterns at some loci or in certain COMPASS mutants.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Many genes do not show the canonical H3K4 methylation gradient pattern </LI> <LI> H3K4 methylation levels are determined by the time Set1 spends near the nucleosome </LI> <LI> Multiple rounds of transcription contribute to H3K4 trimethylation levels </LI> <LI> Set1 fused to RNA pol II places H3K4me2 and H3K4me3 throughout transcribed regions </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>
Heo, Dong-hyuk,Yoo, Inhea,Kong, Jiwon,Lidschreiber, Michael,Mayer, Andreas,Choi, Byung-Yi,Hahn, Yoonsoo,Cramer, Patrick,Buratowski, Stephen,Kim, Minkyu American Society for Biochemistry and Molecular Bi 2013 The Journal of biological chemistry Vol.288 No.51
<P>The RNA polymerase II (RNApII) C-terminal domain (CTD)-interacting domain (CID) proteins are involved in two distinct RNApII termination pathways and recognize different phosphorylated forms of CTD. To investigate the role of differential CTD-CID interactions in the choice of termination pathway, we altered the CTD-binding specificity of Nrd1 by domain swapping. Nrd1 with the CID from Rtt103 (Nrd1(CID<SUP>Rtt103</SUP>)) causes read-through transcription at many genes, but can also trigger termination where multiple Nrd1/Nab3-binding sites and the Ser(P)-2 CTD co-exist. Therefore, CTD-CID interactions target specific termination complexes to help choose an RNApII termination pathway. Interactions of Nrd1 with both CTD and nascent transcripts contribute to efficient termination by the Nrd1 complex. Surprisingly, replacing the Nrd1 CID with that from Rtt103 reduces binding to Rrp6/Trf4, and RNA transcripts terminated by Nrd1(CID<SUP>Rtt103</SUP>) are predominantly processed by core exosome. Thus, the Nrd1 CID couples Ser(P)-5 CTD not only to termination, but also to RNA processing by the nuclear exosome.</P>
Rpd3L HDAC links H3K4me3 to transcriptional repression memory
Lee, Bo Bae,Choi, Ahyoung,Kim, Ji Hyun,Jun, Yukyung,Woo, Hyeonju,Ha, So Dam,Yoon, Chae Young,Hwang, Jin-Taek,Steinmetz, Lars,Buratowski, Stephen,Lee, Sanghyuk,Kim, Hye Young,Kim, TaeSoo Oxford University Press 2018 Nucleic acids research Vol.46 No.16
<P><B>Abstract</B></P><P>Transcriptional memory is critical for the faster reactivation of necessary genes upon environmental changes and requires that the genes were previously in an active state. However, whether transcriptional repression also displays ‘memory’ of the prior transcriptionally inactive state remains unknown. In this study, we show that transcriptional repression of ∼540 genes in yeast occurs much more rapidly if the genes have been previously repressed during carbon source shifts. This novel transcriptional response has been termed transcriptional repression memory (TREM). Interestingly, Rpd3L histone deacetylase (HDAC), targeted to active promoters induces TREM. Mutants for Rpd3L exhibit increased acetylation at active promoters and delay TREM significantly. Surprisingly, the interaction between H3K4me3 and Rpd3L via the Pho23 PHD finger is critical to promote histone deacetylation and TREM by Rpd3L. Therefore, we propose that an active mark, H3K4me3 enriched at active promoters, instructs Rpd3L HDAC to induce histone deacetylation and TREM.</P>