Loss of DNA methylation affects the recombination landscape in Arabidopsis

Abstract

During sexual reproduction, one-half of the genetic material is deposited in gametes, and a complete set of chromosomes is restored upon fertilization. Reduction of the genetic information before gametogenesis occurs in meiosis, when cross-overs (COs) between homologous chromosomes secure an exchange of their genetic information. COs are not evenly distributed along chromosomes and are suppressed in chromosomal regions encompassing compact, hypermethylated centromeric and pericentromeric DNA. Therefore, it was postulated that DNA hypermethylation is inhibitory to COs. Here, when analyzing meiotic recombination in mutant plants with hypomethylated DNA, we observed unexpected and counterintuitive effects of DNA methylation losses on CO distribution. Recombination was further promoted in the hypomethylated chromosome arms while it was inhibited in heterochromatic regions encompassing pericentromeric DNA. Importantly, the total number of COs was not affected, implying that loss of DNA methylation led to a global redistribution of COs along chromosomes. To determine by which mechanisms altered levels of DNA methylation influence recombination-whether directly in cis or indirectly in trans by changing expression of genes encoding recombination components-we analyzed CO distribution in wild-type lines with randomly scattered and wellmapped hypomethylated chromosomal segments. The results of these experiments, supported by expression profiling data, suggest that DNA methylation affects meiotic recombination in cis. Because DNA methylation exhibits significant variation even within a single species, our results imply that it may influence the evolution of plant genomes through the control of meiotic recombination.epigenetic | chromatin | epigenetic recombinant inbred lines | met1-3 R egulation of meiotic recombination, as with other essential chromosomal activities like transcription and replication, depends on both DNA sequence and chromatin properties (1, 2). Although regulatory aspects of meiotic recombination have been studied in great detail, it is still not well understood how chromatin structure influences the frequency and distribution of recombination events, as reflected by the final number and distribution of cross-overs (COs) along chromosomes. Biased chromosomal positioning of COs has been recognized for many years; indeed, COs are most likely to occur in euchromatic chromosomal arms, distal to the recombinationally suppressed pericentromeric heterochromatin. These two chromatin compartments are characterized by differences in the abundance of genes and transposable elements (TEs). TEs accumulate in pericentromeric regions, whereas genes are enriched in distal euchromatin. Because suppressive epigenetic marks are primarily directed at silencing TEs, these two chromatin types also differ in their epigenetic signatures. Pericentromeric chromatin is enriched in the methylation of histone H3 at lysine 9 (H3K9me) and encompasses hypermethylated DNA. In contrast, distal chromatin exhibits active marks such as acet...

Features of the Arabidopsis recombination landscape resulting from the combined loss of sequence variation and DNA methylation

“…3B). However, the presence of the heterochromatic knob on chromosome 4 in the Columbia accession, but not in other accessions, makes this result difficult to interpret (10).…”

“…Specifically, COs were reduced when the recombination interval was methylated on one homolog and were abolished almost completely when methylated on both homologs. In Arabidopsis, two recent mapping studies analyzed F 2 progeny derived from crosses between Columbia ddm1 and met1 [Col(ddm1),Col(met1)] DNA methylation mutants and wild-type Landsberg [Ler(WT)] accessions and showed that loss of DNA methylation could not alleviate the suppression of COs in pericentromeric regions of chromosomes (9,10). However, as pointed out by the authors, this experimental design could not rule out an inhibitory effect of sequence divergence between Col and Ler on COs.…”

High-Resolution Mapping of Crossover Events in the Hexaploid Wheat Genome Suggests a Universal Recombination Mechanism

“…DNA methylation also represses CO formation (Maloisel and Rossignol 1998) and is sufficient to silence CO hotspots in Arabidopsis (Yelina et al 2015). CO distribution is largely modified in Arabidopsis met1 and ddm1 mutants, which show an increase of proximal recombination events and a simultaneous decrease in pericentromeric and distal regions (Colome-Tatche et al 2012;Melamed-Bessudo and Levy 2012;Mirouze et al 2012;Yelina et al 2012). Since H3K4me3 and H2A.Z landmarks are important for promotion of gene transcription (Liu et al 2009;Yelina et al 2012;Choi et al 2013) and are associated with high recombination rates in Arabidopsis (Yelina et al 2012) as well as in barley (Aliyeva-Schnorr et al 2015;Baker et al 2015), this suggests that both recombination and DNA-transposon insertion benefit from low compaction of DNA to occur within the genome.…”

Changes in homologous recombination frequency in Arabidopsis thaliana plants exposed to stress depend on time of exposure during development and on duration of stress exposure

“…HR repairs DNA single-and doublestrand breaks, and the readily accessible regions of homology are required for its activity (Puchta 2005). Stresses that may change the chromatin structure either via changes in DNA methylation or histone modifications may also result in altered HR frequency (Bilichak et al 2012;Endo et al 2006;Gao et al 2012;Kirik et al 2006;Mirouze et al 2012).…”