H2B- and H3-Specific Histone Deacetylases Are Required for DNA Methylation in <i>Neurospora crassa</i>

Smith, Kristina M.; Dobosy, Joseph R.; Reifsnyder, Jennifer; Rountree, Michael R.; Anderson, Dave; Green, George R.; Selker, Eric U.

doi:10.1534/genetics.110.123315

Cited by 43 publications

(54 citation statements)

References 52 publications

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“…Indeed, in some organisms, such as N. crassa, DNA methylation is dependent on the methylation of a particular residue of histone H3, H3K9 (11). Other histone modifications, such as methylation of H3K4, phosphorylation of H3S10 (30,31), and histone acetylation, also influence DNA methylation (32,33). We previously demonstrated that HCHC mutants of N. crassa show increased acetylation of histone H3 and H4 at larger heterochromatin domains, such as centromeres, and speculated that the increased acetylation might provide an enhanced environment for the HP1-DIM-2 complex, leading to the increased DNA methylation observed in the large domains of constitutive heterochromatin in centromere regions.…”

Section: Resultsmentioning

confidence: 99%

Dual chromatin recognition by the histone deacetylase complex HCHC is required for proper DNA methylation in Neurospora crassa

Honda

Bicocca

Gessaman

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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DNA methylation, heterochromatin protein 1 (HP1), histone H3 lysine 9 (H3K9) methylation, histone deacetylation, and highly repeated sequences are prototypical heterochromatic features, but their interrelationships are not fully understood. Prior work showed that H3K9 methylation directs DNA methylation and histone deacetylation via HP1 in Neurospora crassa and that the histone deacetylase complex HCHC is required for proper DNA methylation. The complex consists of the chromodomain proteins HP1 and chromodomain protein 2 (CDP-2), the histone deacetylase HDA-1, and the AT-hook motif protein CDP-2/HDA-1–associated protein (CHAP). We show that the complex is required for proper chromosome segregation, dissect its function, and characterize interactions among its components. Our analyses revealed the existence of an HP1-based DNA methylation pathway independent of its chromodomain. The pathway partially depends on CHAP but not on the CDP-2 chromodomain. CDP-2 serves as a bridge between the recognition of H3K9 trimethylation (H3K9me3) by HP1 and the histone deacetylase activity of HDA-1. CHAP is also critical for HDA-1 localization to heterochromatin. Specifically, the CHAP zinc finger interacts directly with the HDA-1 argonaute-binding protein 2 (Arb2) domain, and the CHAP AT-hook motifs recognize heterochromatic regions by binding to AT-rich DNA. Our data shed light on the interrelationships among the prototypical heterochromatic features and support a model in which dual recognition by the HP1 chromodomain and the CHAP AT-hooks are required for proper heterochromatin formation.

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Section: Resultsmentioning

confidence: 99%

Dual chromatin recognition by the histone deacetylase complex HCHC is required for proper DNA methylation in Neurospora crassa

Honda

Bicocca

Gessaman

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Sustained Hyperacetylation of Histone H3 Results in Arrhythmic Circadian Clock-Previous study has shown that Neurospora RPD-3 affects the acetylation levels of histone H3 on Lys-9, Lys-14, and Lys-18 (45). To test whether histone acetylation at these sites is essential for circadian clock, the histone H3 lysine 9, 14, and 18 were substituted with glutamine to mimic hyperacetylated histone H3.…”

Section: Rpd3s-mediated Deacetylation Of Frq Coding Region Suppressesmentioning

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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“…The cultures were then quenched by the addition of 250 mM glycine for a few minutes, and mycelium was harvested by filtration. About 200 mg of the mycelium was used for subsequent ChIP (49,50). Libraries were prepared as described previously (51).…”

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confidence: 99%

“…Reads were mapped to the F. fujikuroi genome with BurrowsWheeler Aligner and visualized in a gbrowse2 genome browser (50). Quantification of ChIP-seq data was performed by using EpiChIP (49,50,52).…”

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confidence: 99%

Two Histone Deacetylases, FfHda1 and FfHda2, Are Important for Fusarium fujikuroi Secondary Metabolism and Virulence

Studt

Schmidt

Jahn

et al. 2013

Appl Environ Microbiol

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Histone modifications are crucial for the regulation of secondary metabolism in various filamentous fungi. Here we studied the involvement of histone deacetylases (HDACs) in secondary metabolism in the phytopathogenic fungus Fusarium fujikuroi, a known producer of several secondary metabolites, including phytohormones, pigments, and mycotoxins. Deletion of three Zn 2؉ -dependent HDAC-encoding genes, ffhda1, ffhda2, and ffhda4, indicated that FfHda1 and FfHda2 regulate secondary metabolism, whereas FfHda4 is involved in developmental processes but is dispensable for secondary-metabolite production in F. fujikuroi. Single deletions of ffhda1 and ffhda2 resulted not only in an increase or decrease but also in derepression of metabolite biosynthesis under normally repressing conditions. Moreover, double deletion of both the ffhda1 and ffhda2 genes showed additive but also distinct phenotypes with regard to secondary-metabolite biosynthesis, and both genes are required for gibberellic acid (GA)-induced bakanae disease on the preferred host plant rice, as ⌬ffhda1 ⌬ffhda2 mutants resemble the uninfected control plant. Microarray analysis with a ⌬ffhda1 mutant that has lost the major HDAC revealed differential expression of secondarymetabolite gene clusters, which was subsequently verified by a combination of chemical and biological approaches. These results indicate that HDACs are involved not only in gene silencing but also in the activation of some genes. Chromatin immunoprecipitation with the ⌬ffhda1 mutant revealed significant alterations in the acetylation state of secondary-metabolite gene clusters compared to the wild type, thereby providing insights into the regulatory mechanism at the chromatin level. Altogether, manipulation of HDAC-encoding genes constitutes a powerful tool to control secondary metabolism in filamentous fungi.

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H2B- and H3-Specific Histone Deacetylases Are Required for DNA Methylation in Neurospora crassa

Cited by 43 publications

References 52 publications

Dual chromatin recognition by the histone deacetylase complex HCHC is required for proper DNA methylation in Neurospora crassa

Dual chromatin recognition by the histone deacetylase complex HCHC is required for proper DNA methylation in Neurospora crassa

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

Two Histone Deacetylases, FfHda1 and FfHda2, Are Important for Fusarium fujikuroi Secondary Metabolism and Virulence

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