An AP endonuclease functions in active DNA demethylation and gene imprinting in Arabidopsis [corrected]

PLoS Genet. 2015 Jan 8;11(1):e1004905. doi: 10.1371/journal.pgen.1004905. eCollection 2015 Jan.


Active DNA demethylation in plants occurs through base excision repair, beginning with removal of methylated cytosine by the ROS1/DME subfamily of 5-methylcytosine DNA glycosylases. Active DNA demethylation in animals requires the DNA glycosylase TDG or MBD4, which functions after oxidation or deamination of 5-methylcytosine, respectively. However, little is known about the steps following DNA glycosylase action in the active DNA demethylation pathways in plants and animals. We show here that the Arabidopsis APE1L protein has apurinic/apyrimidinic endonuclease activities and functions downstream of ROS1 and DME. APE1L and ROS1 interact in vitro and co-localize in vivo. Whole genome bisulfite sequencing of ape1l mutant plants revealed widespread alterations in DNA methylation. We show that the ape1l/zdp double mutant displays embryonic lethality. Notably, the ape1l+/-zdp-/- mutant shows a maternal-effect lethality phenotype. APE1L and the DNA phosphatase ZDP are required for FWA and MEA gene imprinting in the endosperm and are important for seed development. Thus, APE1L is a new component of the active DNA demethylation pathway and, together with ZDP, regulates gene imprinting in Arabidopsis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Arabidopsis / genetics
  • Arabidopsis / growth & development
  • Arabidopsis Proteins / genetics*
  • Arabidopsis Proteins / metabolism
  • DNA Methylation / genetics*
  • Endonucleases / genetics*
  • Endonucleases / metabolism
  • Endosperm / genetics
  • Endosperm / growth & development
  • Gene Silencing
  • Genome, Plant
  • Genomic Imprinting*
  • High-Throughput Nucleotide Sequencing
  • Homeodomain Proteins / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Seeds / genetics*
  • Seeds / growth & development
  • Transcription Factors / genetics


  • Arabidopsis Proteins
  • FWA protein, Arabidopsis
  • Homeodomain Proteins
  • MEA protein, Arabidopsis
  • Nuclear Proteins
  • ROS1 protein, Arabidopsis
  • Transcription Factors
  • Ape1L protein, Arabidopsis
  • Endonucleases