Publication Date:
2013-05-03
Description:
DNA methylation is an epigenetic modification that has critical roles in gene silencing, development and genome integrity. In Arabidopsis, DNA methylation is established by DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2) and targeted by 24-nucleotide small interfering RNAs (siRNAs) through a pathway termed RNA-directed DNA methylation (RdDM). This pathway requires two plant-specific RNA polymerases: Pol-IV, which functions to initiate siRNA biogenesis, and Pol-V, which functions to generate scaffold transcripts that recruit downstream RdDM factors. To understand the mechanisms controlling Pol-IV targeting we investigated the function of SAWADEE HOMEODOMAIN HOMOLOG 1 (SHH1), a Pol-IV-interacting protein. Here we show that SHH1 acts upstream in the RdDM pathway to enable siRNA production from a large subset of the most active RdDM targets, and that SHH1 is required for Pol-IV occupancy at these same loci. We also show that the SHH1 SAWADEE domain is a novel chromatin-binding module that adopts a unique tandem Tudor-like fold and functions as a dual lysine reader, probing for both unmethylated K4 and methylated K9 modifications on the histone 3 (H3) tail. Finally, we show that key residues within both lysine-binding pockets of SHH1 are required in vivo to maintain siRNA and DNA methylation levels as well as Pol-IV occupancy at RdDM targets, demonstrating a central role for methylated H3K9 binding in SHH1 function and providing the first insights into the mechanism of Pol-IV targeting. Given the parallels between methylation systems in plants and mammals, a further understanding of this early targeting step may aid our ability to control the expression of endogenous and newly introduced genes, which has broad implications for agriculture and gene therapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119789/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119789/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Law, Julie A -- Du, Jiamu -- Hale, Christopher J -- Feng, Suhua -- Krajewski, Krzysztof -- Palanca, Ana Marie S -- Strahl, Brian D -- Patel, Dinshaw J -- Jacobsen, Steven E -- GM60398/GM/NIGMS NIH HHS/ -- GM85394/GM/NIGMS NIH HHS/ -- R01 GM060398/GM/NIGMS NIH HHS/ -- R37 GM060398/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Jun 20;498(7454):385-9. doi: 10.1038/nature12178. Epub 2013 May 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, California 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23636332" target="_blank"〉PubMed〈/a〉
Keywords:
Arabidopsis/*enzymology/genetics/*metabolism
;
Arabidopsis Proteins/chemistry/genetics/*metabolism
;
Binding Sites/genetics
;
Chromatin/chemistry/genetics/metabolism
;
Crystallography, X-Ray
;
DNA Methylation/*genetics
;
DNA-Directed RNA Polymerases/genetics/*metabolism
;
Epigenesis, Genetic/genetics
;
Histones/chemistry/metabolism
;
Homeodomain Proteins/chemistry/*metabolism
;
Lysine/chemistry/metabolism
;
Methyltransferases/genetics/metabolism
;
Models, Molecular
;
Mutation
;
Protein Folding
;
Protein Structure, Tertiary
;
RNA, Small Interfering/biosynthesis/genetics/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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