Epigenome confrontation triggers immediate reprogramming of DNA methylation and transposon silencing in Arabidopsis thaliana F1 epihybrids.

Genes and transposons can exist in variable DNA methylation states, with potentially differential transcription. How these epialleles emerge is poorly understood. Here, we show that crossing an Arabidopsis thaliana plant with a hypomethylated genome and a normally methylated WT individual results, already in the F1 generation, in widespread changes in DNA methylation and transcription patterns. Novel nonparental and heritable epialleles arise at many genic loci, including a locus that itself controls DNA methylation patterns, but with most of the changes affecting pericentromeric transposons. Although a subset of transposons show immediate resilencing, a large number display decreased DNA methylation, which is associated with de novo or enhanced transcriptional activation and can translate into transposon mobilization in the progeny. Our findings reveal that the combination of distinct epigenomes can be viewed as an epigenomic shock, which is characterized by a round of epigenetic variation creating novel patterns of gene and TE regulation.

A novel hereditary extensive vascular leukoencephalopathy mapping to chromosome 20q13.

OBJECTIVE: The detection of a leukoencephalopathy is a frequent situation in neurologic practice. In a number of cases, the etiology remains obscure despite extensive investigations. We characterized the clinical, pathologic, and genetic features of a novel hereditary vascular leukoencephalopathy. METHODS: After the observation of a similar leukoencephalopathy in 2 sisters, clinical, neuroimaging, and molecular genetics investigations were conducted in 21 of their consenting relatives. Pathologic data were obtained in one patient. RESULTS: Fourteen members presented with significant white matter lesions at MRI examination, among whom only 5 individuals were symptomatic. The main clinical manifestations included gait disturbances, transient movement disorders, stroke, and cognitive dysfunction. The 9 remaining members aged from 26 to 60 years were asymptomatic. The MRI pattern was highly stereotyped with symmetric white matter hyperintensities worsening with patient's age. We mapped the gene involved in this condition on chromosome 20q13. Neuropathologic examination suggested that this leukoencephalopathy is underlaid by a cerebral arteriolopathy affecting small preterminal arterioles, clearly distinct from amyloid angiopathy and hypertension-related small-vessel disease. CONCLUSIONS: These data establish that this family is affected by a novel autosomal dominant vascular leukoencephalopathy mapping to chromosome 20q13. This disease is characterized by a progressive and age-related hemispheric and brainstem leukoencephalopathy contrasting with the paucity and late onset of clinical symptoms in most of the cases.

DNA methylation in an intron of the IBM1 histone demethylase gene stabilizes chromatin modification patterns.

The stability of epigenetic patterns is critical for genome integrity and gene expression. This highly coordinated process involves interrelated positive and negative regulators that impact distinct epigenetic marks, including DNA methylation and dimethylation at histone H3 lysine 9 (H3K9me2). In Arabidopsis, mutations in the DNA methyltransferase MET1, which maintains CG methylation, result in aberrant patterns of other epigenetic marks, including ectopic non-CG methylation and the relocation of H3K9me2 from heterochromatin into gene-rich chromosome regions. Here, we show that the expression of the H3K9 demethylase IBM1 (increase in BONSAI methylation 1) requires DNA methylation. Surprisingly, the regulatory methylated region is contained in an unusually large intron that is conserved in IBM1 orthologues. The re-establishment of IBM1 expression in met1 mutants restored the wild-type H3K9me2 nuclear patterns, non-CG DNA methylation and transcriptional patterns at selected loci, which included DNA demethylase genes. These results provide a mechanistic explanation for long-standing puzzling observations in met1 mutants and reveal yet another layer of control in the interplay between DNA methylation and histone modification, which stabilizes DNA methylation patterns at genes.

Sjögren-Larsson syndrome: novel mutations in the ALDH3A2 gene in a French cohort.

Sjogren-Larsson syndrome (SLS) is a rare autosomal recessive disorder characterized by ichthyosis, spastic di- or tetraplegia and mental retardation due a defect of the fatty aldehyde dehydrogenase (FALDH), related to mutations in the ALDH3A2 gene. In this study, we screened a French cohort of patients with Sjögren-Larsson syndrome (SLS) for mutations in the ALDH3A2 gene. The five unrelated patients with typical SLS all present mutations in this gene. Three novel mutations were identified whereas three other ones were previously described. We also realized functional analyses at the mRNA level for two splice site mutations to study their deleterious consequences. Two of the previously described mutations had already been identified in the same region of Europe, suggesting a putative founder effect. We suggest that, (1) when clinical and MR features are present, direct sequencing of the ALDH3A2 gene in SLS is of particular interest without necessity of a skin biopsy for enzymatic assay in order to propose genetic counsel and (2) identification of mutations already described in the same population with putative founder effects may simplify genetic analysis in this context.

A "mille-feuille" of silencing: epigenetic control of transposable elements.

Despite their abundance in the genome, transposable elements (TEs) and their derivatives are major targets of epigenetic silencing mechanisms, which restrain TE mobility at different stages of the life cycle. DNA methylation, post-translational modification of histone tails and small RNA-based pathways contribute to maintain TE silencing; however, some of these epigenetic marks are tightly interwoven and this complicates the delineation of the exact contribution of each in TE silencing. Recent studies have confirmed that host genomes have evolved versatility in the use of these mechanisms to individualize silencing of particular TEs. These studies also revealed that silencing of TEs is much more dynamic than had been previously thought and can be reversed on the genomic scale in particular cell types or under special environmental conditions. This article is part of a Special Issue entitled "Epigenetic control of cellular and developmental processes in plants".