Unknown,Transcriptomics,Genomics,Proteomics

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Loss of DNA methylation affects recombination landscape in Arabidopsis

ABSTRACT: During sexual reproduction half of the genetic material is deposited in gametes and a complete set of chromosomes is restored upon fertilisation. Reduction of the genetic information prior gametogenesis occurs in meiosis where crossovers (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 has been postulated that DNA hypermethylation is inhibitory to COs. Here by analysing meiotic recombination in mutant plants with hypomethylated DNA we observed unexpected and counterintuitive effects of the DNA methylation losses on COs distribution, further promoting recombination in the naturally hypomethylated euchromatic chromosome arms, while inhibiting it in heterochromatic regions encompassing centromeric and pericentromeric hypermethylated DNA. Importantly, the total number of COs was not affected, implying that the loss of DNA methylation only led to a global redistribution of COs along chromosomes. To determine by which mechanisms altered levels of DNA methylation influenced recombination, namely whether this occurred directly in cis or indirectly in trans by changing expression of genes encoding recombination components, we analysed COs distribution in WT lines with randomly scattered and well mapped hypomethylated chromosomal segments. Results of these experiments, supported by expression profiling data, suggest that DNA methylation affects meiotic recombination in cis. As DNA methylation is subjected to significant variation even within a single species, our results implicate that it could influence evolution of plant genomes through the control of meiotic recombination. 2 samples: Col, epiRIL12, with 3 replicates each

ORGANISM(S): Arabidopsis thaliana

SUBMITTER: Etienne Bucher

PROVIDER: E-GEOD-34173 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Immunodeficiency, centromeric instability and facial anomalies syndrome (ICF) is a rare autosomal recessive disease, characterized by severe hypomethylation in pericentromeric regions of chromosomes (1, 16 and 9), marked immunodeficiency and facial anomalies. The majority of ICF patients present mutations in the DNMT3B gene, affecting the DNA methyltransferase activity of the protein. In the present study, we have used the Infinium 450K DNA methylation array to evaluate the methylation level of 450,000 CpGs in lymphoblastoid cell lines and untrasformed fibroblasts derived from ICF patients and healthy donors. Our results demonstrate that ICF-specific DNMT3B variants A603T/STP807ins and V699G/R54X cause global DNA hypomethylation compared to wild-type protein. We identified 181 novel differentially methylated positions (DMPs) including subtelomeric and intrachromosomic regions, outside the classical ICF-related pericentromeric hypomethylated positions. Interestingly, these sites were mainly located in intergenic regions and inside the CpG islands. Among the identified hypomethylated CpG-island associated genes, we confirmed the overexpression of three selected genes, BOLL, SYCP2 and NCRNA00221, in ICF compared to healthy controls, which are normally expressed in germ line and silenced in somatic tissues. In conclusion, this study contributes in clarifying the direct relationship between DNA methylation defect and gene expression impairment in ICF syndrome, identifying novel direct target genes of DNMT3B. A high percentage of the DMPs are located in the subtelomeric regions, indicating a specific role of DNMT3B in methylating these chromosomal sites. Therefore, we provide further evidence that hypomethylation in specific non-pericentromeric regions of chromosomes might be involved in the molecular pathogenesis of ICF syndrome. The detection of DNA hypomethylation at BOLL, SYCP2 and NCRNA00221 may pave the way for the development of specific clinical biomarkers with the aim to facilitate the identification of ICF patients.

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Loss of DNA methylation affects recombination landscape in Arabidopsis

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