title: Folate polyglutamylation is involved in chromatin silencing by maintaining global DNA methylation and histone H3K9 dimethylation in Arabidopsis.
abstract: DNA methylation and repressive histone Histone3 Lysine9 (H3K9) dimethylation correlate with chromatin silencing in plants and mammals. To identify factors required for DNA methylation and H3K9 dimethylation, we screened for suppressors of the repressor of silencing1 (ros1) mutation, which causes silencing of the expression of the RD29A (RESPONSE TO DESSICATION 29A) promoter-driven luciferase transgene (RD29A-LUC) and the 35S promoter-driven NPTII (NEOMYCIN PHOSPHOTRANSFERASE II) transgene (35S-NPTII). We identified the folylpolyglutamate synthetase FPGS1 and the known factor DECREASED DNA METHYLATION1 (DDM1). The fpgs1 and ddm1 mutations release the silencing of both RD29A-LUC and 35S-NPTII. Genome-wide analysis indicated that the fpgs1 mutation reduces DNA methylation and releases chromatin silencing at a genome-wide scale. The effect of fpgs1 on chromatin silencing is correlated with reduced levels of DNA methylation and H3K9 dimethylation. Supplementation of fpgs1 mutants with 5-formyltetrahydrofolate, a stable form of folate, rescues the defects in DNA methylation, histone H3K9 dimethylation, and chromatin silencing. The competitive inhibitor of methyltransferases, S-adenosylhomocysteine, is markedly upregulated in fpgs1, by which fpgs1 reduces S-adenosylmethionine accessibility to methyltransferases and accordingly affects DNA and histone methylation. These results suggest that FPGS1-mediated folate polyglutamylation is required for DNA methylation and H3K9 dimethylation through its function in one-carbon metabolism. Our study makes an important contribution to understanding the complex interplay among metabolism, development, and epigenetic regulation.
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Hao-Ran
authors.initials: HR
authors.lastname: Zhou
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Zhang
authors.forename: Ze-Yang
authors.initials: ZY
authors.lastname: Ma
authors.forename: Huan-Wei
authors.initials: HW
authors.lastname: Huang
authors.forename: Ling
authors.initials: L
authors.lastname: Jiang
authors.forename: Tao
authors.initials: T
authors.lastname: Cai
authors.forename: Jian-Kang
authors.initials: JK
authors.lastname: Zhu
authors.forename: Chuyi
authors.initials: C
authors.lastname: Zhang
authors.forename: Xin-Jian
authors.initials: XJ
authors.lastname: He
mesh_terms: D017360:Arabidopsis / Q000235:genetics* / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D032461:Chromosomes, Plant / Q000235:genetics; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005492:Folic Acid / Q000378:metabolism; D018506:Gene Expression Regulation, Plant; D020868:Gene Silencing; D005816:Genetic Complementation Test; D006657:Histones / Q000378:metabolism*; D015151:Immunoblotting; D019868:Kanamycin Kinase / Q000235:genetics / Q000378:metabolism; D008239:Lysine; D008745:Methylation; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010453:Peptide Synthases / Q000235:genetics* / Q000378:metabolism; D030821:Plants, Genetically Modified; D011099:Polyglutamic Acid / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D029681:Arabidopsis Proteins; D002843:Chromatin; C118957:DDM1 protein, Arabidopsis; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; C520629:RD29a protein, Arabidopsis; C471271:ROS1 protein, Arabidopsis; D014157:Transcription Factors; D011099:Polyglutamic Acid; D005492:Folic Acid; D019868:Kanamycin Kinase; D010453:Peptide Synthases; C023103:folylpolyglutamate synthetase; D008239:Lysine