Cytosine methylation at CpCpG sites triggers accumulation of non-CpG methylation in gene bodies

Research output: Contribution to journalArticlepeer-review


  • Nicolae Radu Zabet
  • Marco Catoni
  • Filippo Prischi
  • Jerzy Paszkowski

Colleges, School and Institutes

External organisations

  • University of Essex
  • University of Cambridge


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.


Original languageEnglish
Pages (from-to)3777-3784
Number of pages8
JournalNucleic Acids Research
Issue number7
Early online date4 Jan 2017
Publication statusPublished - 20 Apr 2017


  • Arabidopsis/genetics, Arabidopsis Proteins/genetics, CpG Islands, Cytosine/metabolism, DNA Methylation, Epigenesis, Genetic, Gene Expression Regulation, Plant, Genes, Plant, Jumonji Domain-Containing Histone Demethylases/genetics