Chromatin remodelers Isw1 and Chd1 maintain chromatin structure during transcription by preventing histone exchange

Smolle, Michaela; Venkatesh, Swaminathan; Gogol, Madelaine; Li, Hua; Zhang, Ying; Florens, Laurence; Washburn, Michael P.; Workman, Jerry L.

doi:10.1038/nsmb.2312

Cited by 271 publications

(359 citation statements)

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“…Chromatin is quickly reassembled after passing through the transcription machinery (59,60), and hyperacetylation or lack of chromatin remodelers induces cryptic bidirectional transcription by Pol II (61,62). It would be interesting to explore whether Pol III also contributes to these cryptic bidirectional transcripts.…”

Section: Discussionmentioning

confidence: 99%

RNA Polymerase III Accurately Initiates Transcription from RNA Polymerase II Promoters in Vitro

Duttke

2014

Journal of Biological Chemistry

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Background: RNA polymerase II (Pol II) and III (Pol III) transcription systems are reported to regulate non-overlapping sets of genes. Results: Pol III can initiate transcription from Pol II promoters with AT-rich sequence. The DNA template to nuclear extract ratio determines the predominant polymerase. Conclusion: Pol II and Pol III transcription initiation can overlap. Significance: RNA polymerase specificity is variable and depends on the transcription conditions.

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Section: Discussionmentioning

confidence: 99%

RNA Polymerase III Accurately Initiates Transcription from RNA Polymerase II Promoters in Vitro

Duttke

2014

Journal of Biological Chemistry

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“…In Saccharomyces cerevisiae, Set2-mediated H3K36me3 maintains a hypoacetylation state of transcribed genes (28,29,31,32), especially for genes with long sequence and transcribed less often (44). Based on these studies, we wondered whether SET-2 affects the histone acetylation level at frq locus.…”

Section: Deletion Of Set-2 Results In Hyperacetylation Of Frq Open Rementioning

confidence: 99%

Suppression of WHITE COLLAR-independent frequency Transcription by Histone H3 Lysine 36 Methyltransferase SET-2 Is Necessary for Clock Function in Neurospora

Sun

Zhou

Xiao

et al. 2016

Journal of Biological Chemistry

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The circadian system in Neurospora is based on the transcriptional/translational feedback loops and rhythmic frequency (frq) transcription requires the WHITE COLLAR (WC) complex. Our previous paper has shown that frq could be transcribed in a WC-independent pathway in a strain lacking the histone H3K36 methyltransferase, SET-2 (su(var)3-9-enhancer-of-zestetrithorax-2) (1), but the mechanism was unclear. Here we disclose that loss of histone H3K36 methylation, due to either deletion of SET-2 or H3K36R mutation, results in arrhythmic frq transcription and loss of overt rhythmicity. Histone acetylation at frq locus increases in set-2 KO mutant. Consistent with these results, loss of H3K36 methylation readers, histone deacetylase RPD-3 (reduced potassium dependence 3) or EAF-3 (essential SAS-related acetyltransferase-associated factor 3), also leads to hyperacetylation of histone at frq locus and WC-independent frq expression, suggesting that proper chromatin modification at frq locus is required for circadian clock operation. Furthermore, a mutant strain with three amino acid substitutions (histone H3 lysine 9, 14, and 18 to glutamine) was generated to mimic the strain with hyperacetylation state of histone H3. H3K9QK14QK18Q mutant exhibits the same defective clock phenotype as rpd-3 KO mutant. Our results support a scenario in which H3K36 methylation is required to establish a permissive chromatin state for circadian frq transcription by maintaining proper acetylation status at frq locus.Despite evolutionary distance, circadian clock oscillators are conserved among the organisms to perform their cellular and behavioral activities. The eukaryotic circadian clock oscillator contains positive and negative elements that form auto-regulatory negative feedback loops (2-8).In the Neurospora circadian negative feedback loop, the GATA-family transcription factors WHITE COLLAR-1 (WC-1) 3 and WHITE COLLAR-2 (WC-2) serve as positive elements. Typically, WC-1 and WC-2 form a heterodimer through their Per-Arnt-Sim (PAS) domain and rhythmically bind the promoter of the clock gene frequency (frq) to activate its transcription. FREQUENCY (FRQ) and its partner FRQ-interacting RNA helicase (FRH) act as negative elements. FRQ is the core factor in Neurospora oscillator, which determines the normal clock rhythm (9 -16). The translated FRQ interacts with FRH and forms the FFC (FRQ-FRH complex) to inhibit its own transcription by suppressing the activity of the WC complex. FRQ is progressively phosphorylated and degraded through the ubiquitin-proteasome pathway. Degradation of FRQ derepresses the WC complex, initiating a new circle of frq transcription (14,(17)(18)(19). The circadian oscillator creates a robust rhythmic system with a period of ϳ22 h in Neurospora crassa (17,20). Rhythmic activation and repression of frq transcription result in cyclic changes of frq mRNA abundance. In Neurospora, histone modifiers and chromatin remodelers are required for rhythmic transcription of frq gene and clock-controlled genes (1, 9, 22-24). Howeve...

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“…It is conceivable that the role of H3K36me2 in splicing is directly connected to the ability of this mark to maintain a suppressed chromatin environment through the recruitment of Rpd3S and Isw1b. [37][38][39][40][41] Indeed, deletion of RPD3, which encodes a member of the Rpd3 complex, 75-77 also leads to modest splicing defects, which could imply that histone deacetylation and chromatin remodeling (i.e., creation of a particular chromatin environment) plays a key role in snRNP recruitment. Another possibility is the potential role of H3K36 methylation in affecting some aspect of RNA Pol II elongation or termination.…”

Section: Discussionmentioning

confidence: 99%

“…36 Studies show that Set2 is associated with the elongating form of RNA Pol II and mediates H3K36me2/me3 to recruit a number of chromatin-modifying complexes (Rpd3S and Isw1b) that maintain a repressive chromatin environment that is resistant to pervasive transcription in the coding regions of genes. [37][38][39][40][41][42] Although a number of studies have shown that the human homolog of Set2, SETD2, is important for alternative splicing 31,33 and that H3K36 is essential for viability in drosophila, 43 the direct role of H3K36me3 and other methylation states (particularly H3K36me2) in both canonical and alternative splicing has not been clearly elucidated.…”

Section: Introductionmentioning

confidence: 99%

Histone H3K36 methylation regulates pre-mRNA splicing inSaccharomyces cerevisiae

et al. 2016

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Co-transcriptional splicing takes place in the context of a highly dynamic chromatin architecture, yet the role of chromatin restructuring in coordinating transcription with RNA splicing has not been fully resolved. To further define the contribution of histone modifications to pre-mRNA splicing in Saccharomyces cerevisiae, we probed a library of histone point mutants using a reporter to monitor pre-mRNA splicing. We found that mutation of H3 lysine 36 (H3K36) -a residue methylated by Set2 during transcription elongation -exhibited phenotypes similar to those of pre-mRNA splicing mutants. We identified genetic interactions between genes encoding RNA splicing factors and genes encoding the H3K36 methyltransferase Set2 and the demethylase Jhd1 as well as point mutations of H3K36 that block methylation. Consistent with the genetic interactions, deletion of SET2, mutations modifying the catalytic activity of Set2 or H3K36 point mutations significantly altered expression of our reporter and reduced splicing of endogenous introns. These effects were dependent on the association of Set2 with RNA polymerase II and H3K36 dimethylation. Additionally, we found that deletion of SET2 reduces the association of the U2 and U5 snRNPs with chromatin. Thus, our study provides the first evidence that H3K36 methylation plays a role in co-transcriptional RNA splicing in yeast.Abbreviations: (H3K36), histone H3 lysine 36; (ChIP), chromatin immunoprecipitations; (RT-qPCR), reverse transcription PCR; (snRNP), small nuclear ribonucleprotein; (RNA Pol II), RNA polymerase II

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Chromatin remodelers Isw1 and Chd1 maintain chromatin structure during transcription by preventing histone exchange

Cited by 271 publications

References 50 publications

RNA Polymerase III Accurately Initiates Transcription from RNA Polymerase II Promoters in Vitro

RNA Polymerase III Accurately Initiates Transcription from RNA Polymerase II Promoters in Vitro

Suppression of WHITE COLLAR-independent frequency Transcription by Histone H3 Lysine 36 Methyltransferase SET-2 Is Necessary for Clock Function in Neurospora

Histone H3K36 methylation regulates pre-mRNA splicing inSaccharomyces cerevisiae

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