Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation.

By K. Nishioka, S. Chuikov, K. Sarma, H. Erdjument‐Bromage, C. D. Allis, Paul Tempst, D. Reinberg. Genes & Development, 2002

599 citations recorded by the source corpus.

A novel histone methyltransferase, termed Set9, was isolated from human cells. Set9 contains a SET domain, but lacks the pre- and post-SET domains. Set9 methylates specifically lysine 4 (K4) of histone H3 (H3-K4) and potentiates transcription activation. The histone H3 tail interacts specifically with the histone deacetylase NuRD complex. Methylation of histone H3-K4 by Set9 precludes the association of NuRD with the H3 tail. Moreover, methylation of H3-K4 impairs Suv39h1-mediated methylation at K9 of H3 (H3-K9). The interplay between the Set9 and Suv39h1 histone methyltransferases is specific, as the methylation of H3-K9 by the histone methyltransferase G9a was not affected by Set9 methylation of H3-K4. Our studies suggest that Set9-mediated methylation of H3-K4 functions in transcription activation by competing with histone deacetylases and by precluding H3-K9 methylation by Suv39h1. Our results suggest that the methylation of histone tails can have distinct effects on transcription, depending on its chromosomal location, the combination of posttranslational modifications, and the enzyme (or protein complex) involved in the particular modification.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3d6f854d55be7af9507cffde8c51eb361714228f

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In Molecular Biology

1. D. Reinberg
2. C. D. Allis
3. Yi Zhang
4. T. Jenuwein
5. Paul Tempst
6. H. Erdjument‐Bromage
7. M. Lachner
8. W. Fischle

Citations in the corpus

• Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain. (2002, unknown): “have been reported [6–14].”
• Candida albicans Infection Affords Protection against Reinfection via Functional Reprogramming of Monocytes (2012, background): “Importantly, β-glucan also induced increased gene expression of several histone methyltransferases after training, including SETD7, which has been previously related to H3K4me3 (Nishioka et al., 2002) (Figure 4K).”
• A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin. (2004, methodology): “An alignment of all SET domains and the neighbor-joining tree was created by using the t-coffee alignment program (Notredame et al. 2000).”
• Histone and chromatin cross-talk. (2003, background): “Such ‘exclusion/repulsion’ has been shown in the case of methylation of H3 on K4, which results in reduced binding of a chromatin repressor complex to the H3 tail [57,58].”
• An epigenetic road map for histone lysine methylation (2003, background): “Recruitment of several H3-K9-specific HMTases induces gene repression within euchromatin (Tachibana et al., 2001; Nielsen et al., 2001; Vandel et al., 2001; Ogawa et al., 2002; Schultz et al., 2002; Tachibana et al., 2002; Yang et al., 2002).”
• SIRTUIN 1 AND SIRTUIN 3: PHYSIOLOGICAL MODULATORS OF METABOLISM (2012, background): “Set7 is known to stimulate activator-induced transcription in vivo (234), and one of these transcription factors might be p53.”
• Human SWI/SNF-Associated PRMT5 Methylates Histone H3 Arginine 8 and Negatively Regulates Expression of ST7 and NM23 Tumor Suppressor Genes (2004, background): “For example, methylation of H3 lysine 4 (H3K4) by either SET7 or SET9 can activate transcription (30, 50), while methylation of H3K9 by either SUV39H1 or G9a can induce binding of heterochromatin protein 1 and promote transcriptional silencing by triggering the formation of heterochromatin (1, 22, 2”
• Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. (2002, methodology): “…SUV39H (Rea et al. 2000), G9A (Tachibana et al. 2001), ESET (Yang et al. 2002), Set9 (Nishioka et al. 2002a; Wang et al. 2001a), and PR-Set7 (Nishioka et al. 2002b), and the yeast proteins Set1 (Briggs et al. 2001) and Set2 (Strahl et al. 2002)—were shown to possess lysine-specific HMT…”
• Elongation by RNA polymerase II: the short and long of it. (2004, background): “Experiments designed to understand how methylation at H3-K4 positively affects transcription revealed that the histone deacetylase NuRD complex binds to the H3 tail in the absence of H3-K4 methylation (Nishioka et al. 2002; Zegerman et al. 2002), thus maintaining a deacetylated state of the tail.”
• Regulation of p53 activity through lysine methylation (2004, background): “Recently, we identified a histone methyltransferase, Set9, that targets histone H3 at lysine 4 and showed that this modification is associated with gene activatio”
• Recognition of trimethylated histone H3 lysine 4 facilitates the recruitment of transcription postinitiation factors and pre-mRNA splicing. (2007, result): “The related chromodomain containing ATPase CHD3 did not associate with H3K4me3 peptides, a finding supported by previous studies (Figure 1B) (Nishioka et al., 2002; Zegerman et al., 2002).”