title: Cytosine methylation at CpCpG sites triggers accumulation of non-CpG methylation in gene bodies.
abstract: Methylation of cytosine is an epigenetic mark involved in the regulation of transcription, usually associated with transcriptional repression. In mammals, methylated cytosines are found predominantly in CpGs but in plants non-CpG methylation (in the CpHpG or CpHpH contexts, where H is A, C or T) is also present and is associated with the transcriptional silencing of transposable elements. In addition, CpG methylation is found in coding regions of active genes. In the absence of the demethylase of lysine 9 of histone 3 (IBM1), a subset of body-methylated genes acquires non-CpG methylation. This was shown to alter their expression and affect plant development. It is not clear why only certain body-methylated genes gain non-CpG methylation in the absence of IBM1 and others do not. Here we describe a link between CpG methylation and the establishment of methylation in the CpHpG context that explains the two classes of body-methylated genes. We provide evidence that external cytosines of CpCpG sites can only be methylated when internal cytosines are methylated. CpCpG sites methylated in both cytosines promote spreading of methylation in the CpHpG context in genes protected by IBM1. In contrast, CpCpG sites remain unmethylated in IBM1-independent genes and do not promote spread of CpHpG methylation.
authors.affiliation: The Sainsbury Laboratory, University of Cambridge, Cambridge, CB2 1LR, UK.|School of Biological Sciences, University of Essex, Colchester, CO4 3SQ, UK.
authors.forename: Nicolae Radu
authors.initials: NR
authors.lastname: Zabet
authors.affiliation: The Sainsbury Laboratory, University of Cambridge, Cambridge, CB2 1LR, UK.
authors.forename: Marco
authors.initials: M
authors.lastname: Catoni
authors.affiliation: School of Biological Sciences, University of Essex, Colchester, CO4 3SQ, UK.
authors.forename: Filippo
authors.initials: F
authors.lastname: Prischi
authors.affiliation: The Sainsbury Laboratory, University of Cambridge, Cambridge, CB2 1LR, UK.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Paszkowski
mesh_terms: D017360:Arabidopsis / Q000235:genetics / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000235:genetics; D018899:CpG Islands; D003596:Cytosine / Q000378:metabolism*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D018506:Gene Expression Regulation, Plant; D017343:Genes, Plant; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics
chemical_list: D029681:Arabidopsis Proteins; D003596:Cytosine; C526313:IBM1 protein, Arabidopsis; D056484:Jumonji Domain-Containing Histone Demethylases