SRA-and SET-domain-containing proteins link RNA polymerase v occupancy to DNA methylation Journal Article
| Authors: | Johnson, L. M.; Du, J.; Hale, C. J.; Bischof, S.; Feng, S.; Chodavarapu, R. K.; Zhong, X.; Marson, G.; Pellegrini, M.; Segal, D. J.; Patel, D. J.; Jacobsen, S. E. |
| Article Title: | SRA-and SET-domain-containing proteins link RNA polymerase v occupancy to DNA methylation |
| Abstract: | RNA-directed DNA methylation in Arabidopsis thaliana depends on the upstream synthesis of 24-nucleotide small interfering RNAs (siRNAs) by RNA POLYMERASE IV (Pol IV) and downstream synthesis of non-coding transcripts by Pol V. Pol V transcripts are thought to interact with siRNAs which then recruit DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2) to methylate DNA. The SU(VAR)3-9 homologues SUVH2 and SUVH9 act in this downstream step but the mechanism of their action is unknown. Here we show that genome-wide Pol V association with chromatin redundantly requires SUVH2 and SUVH9. Although SUVH2 and SUVH9 resemble histone methyltransferases, a crystal structure reveals that SUVH9 lacks a peptide-substrate binding cleft and lacks a properly formed S-adenosyl methionine (SAM)-binding pocket necessary for normal catalysis, consistent with a lack of methyltransferase activity for these proteins. SUVH2 and SUVH9 both contain SRA (SET-and RING-ASSOCIATED) domains capable of binding methylated DNA, suggesting that they function to recruit Pol V through DNA methylation. Consistent with this model, mutation of DNA METHYLTRANSFERASE 1 (MET1) causes loss of DNA methylation, a nearly complete loss of Pol V at its normal locations, and redistribution of Pol V to sites that become hypermethylated. Furthermore, tethering SUVH2 with a zinc finger to an unmethylated site is sufficient to recruit Pol V and establish DNA methylation and gene silencing. These results indicate that Pol V is recruited to DNA methylation through the methyl-DNA binding SUVH2 and SUVH9 proteins, and our mechanistic findings suggest a means for selectively targeting regions of plant genomes for epigenetic silencing. © 2014 Macmillan Publishers Limited. |
| Keywords: | unclassified drug; dna binding protein; methylation; mutation; dna-binding proteins; binding affinity; polymerase chain reaction; protein domain; phenotype; protein; rna, small interfering; genetic association; transcription, genetic; enzyme activity; dna methylation; rna; methyltransferase; dna; histone methyltransferase; chromatin; histone-lysine n-methyltransferase; protein transport; genome; crystal structure; models, molecular; crystallography, x-ray; protein structure, tertiary; binding sites; herb; gene silencing; catalysis; enzyme localization; dna methyltransferase 1; dna (cytosine-5-)-methyltransferase; biocatalysis; dna-directed rna polymerases; rna polymerase; arabidopsis; zinc fingers; s adenosylmethionine; homology; arabidopsis thaliana; arabidopsis proteins; gene expression regulation, plant; genome, plant; rna, plant; plant genome; flowers; priority journal; article; protein suvh2; protein suvh9; rna polymerase v |
| Journal Title: | Nature |
| Volume: | 507 |
| Issue: | 7490 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2014-03-06 |
| Start Page: | 124 |
| End Page: | 128 |
| Language: | English |
| DOI: | 10.1038/nature12931 |
| PUBMED: | 24463519 |
| PROVIDER: | scopus |
| PMCID: | PMC3963826 |
| DOI/URL: | |
| Notes: | Cited By (since 1996):4 -- Export Date: 1 August 2014 -- CODEN: NATUA -- Source: Scopus |
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