AXR1 affects DNA methylation independently of its role in regulating meiotic crossover localization.

Nicolas Christophorou,Aurélie Chambon,Nicolas Bouché,Victor Solier,Wenjing She,Xiaoqi Feng,Jincheng Long,Yassir Idir,Marina Tagliaro-Jahns,Sébastien Beaubiat,Daniel Vezon,Mathilde Grelon,Aurélie Hurel,Christine Mézard

doi:10.1371/journal.pgen.1008894

Abstract

Meiotic crossovers (COs) are important for reshuffling genetic information between homologous chromosomes and they are essential for their correct segregation. COs are unevenly distributed along chromosomes and the underlying mechanisms controlling CO localization are not well understood. We previously showed that meiotic COs are mis-localized in the absence of AXR1, an enzyme involved in the neddylation/rubylation protein modification pathway in Arabidopsis thaliana. Here, we report that in axr1-/-, male meiocytes show a strong defect in chromosome pairing whereas the formation of the telomere bouquet is not affected. COs are also redistributed towards subtelomeric chromosomal ends where they frequently form clusters, in contrast to large central regions depleted in recombination. The CO suppressed regions correlate with DNA hypermethylation of transposable elements (TEs) in the CHH context in axr1-/- meiocytes. Through examining somatic methylomes, we found axr1-/- affects DNA methylation in a plant, causing hypermethylation in all sequence contexts (CG, CHG and CHH) in TEs. Impairment of the main pathways involved in DNA methylation is epistatic over axr1-/- for DNA methylation in somatic cells but does not restore regular chromosome segregation during meiosis. Collectively, our findings reveal that the neddylation pathway not only regulates hormonal perception and CO distribution but is also, directly or indirectly, a major limiting pathway of TE DNA methylation in somatic cells.

Highlights

Meiosis is a specialized type of cell division that produces haploid spores that eventually develop into gametes
We did not detect any significant difference in the number of chromatids with 0, 1, 2 or more COs in axr1-/- compared to wild type (S1 Fig)
The CO rate was significantly different in 18 genetic intervals (Benjamini, Krieger and Yekutieli, with Q = 1%) between the wild type and the axr1-/- mutant: four intervals were either immediately adjacent or very close to telomeres with a large increase in CO rates in the mutant whereas the others were proximal with lower CO rates in axr1-/- compared to wild type (Fig 1B, S1 Table)

Summary

Introduction

Meiosis is a specialized type of cell division that produces haploid spores that eventually develop into gametes. It requires a single round of DNA replication followed by two successive rounds of chromosome segregation. Two different pathways contribute to CO formation: class I COs depend on the ZMM proteins (Zip, Zip, Zip, Zip, Msh, Msh, Spo and Mer3), in addition to Mlh and Mlh. Two different pathways contribute to CO formation: class I COs depend on the ZMM proteins (Zip, Zip, Zip, Zip, Msh, Msh, Spo and Mer3), in addition to Mlh and Mlh3 Their distribution is affected by interference (adjacent COs are more regularly spaced than expected if they were randomly distributed [2]). Class II COs depend notably on the Mus81/Eme protein complex and do not interfere (reviewed in [3])

Methods

Results

Conclusion