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Chouaref, J.

Publications and source records attributed to Chouaref, J..

4 recordsLinked to original sources

AT-HOOK-MOTIF NUCLEAR LOCALIZED 15 extends plant longevity by binding at poorly accessible, epigenetic mark-depleted chromatin that surrounds transcribed regions

BackgroundMembers of the AT-HOOK MOTIF NUCLEAR LOCALIZED (AHL) gene family have been shown to play important roles in plant development. In Arabidopsis thaliana, one member of this family, AHL15, induces somatic embryogenesis and extends plant longevity when overexpressed - the latter through strong repression of several ageing-related developmental transitions. However, its direct target genes and the mechanisms by which it regulates their expression have remained elusive to date. ResultsIn this study we identified the genome-wide DNA binding sites of AHL15 and show that AHL15 binds throughout the genome at AT-rich sequences near the transcription start- and end sites in regions depleted of epigenetic marks. We show that induction of AHL15 activity causes strong and rapid changes in transcription, with the majority of the differentially expressed genes being downregulated but without directly affecting chromatin accessibility, resulting in developmental defects. In addition, AHL15 binding to regions near the transcription start and end sites was enhanced at genes that were differentially expressed upon AHL15 induction and was especially strong near the transcription start site of upregulated genes and near the transcription end site of downregulated genes. Finally, we show that AHL15 shares binding sites with the chromatin architectural protein GH1-HMGA2/HON5, which was previously shown to alter transcription by disrupting gene loop formation. ConclusionsTogether, our findings suggest that AHL15 affects the expression of its target genes by regulating the 3D organization rather than by changing the accessibility of chromatin or the deposition of histone modifications.

plant biology↗

The epigenetic reader MORC3 is required for T cell development in the thymus

Cell fate decisions are orchestrated by an interplay of epigenetic factors in collaboration with transcriptional activators and repressors. The epigenetic reader MORC3 is known as a silencer of endogenous retroviruses in mouse embryonic stem cells. Here, we show that mouse MORC3 is expressed in the thymus and reveal that MORC3 loss of function leads to a severe arrest in T cell development at the DN1 stage, accompanied by an expansion of natural killer and myeloid cells. MORC3 function in thymus depends on its ATPase and its ability to bind H3K4me via the CW-type zinc finger domain. We find altered chromatin accessibility at regulatory elements of key T cell transcription factors in DN1 cells and show that re-expressing TCF1 in MORC3-deficient progenitor cells, rescues T cell development. Our work indicates a novel function for MORC3 in modulating regulatory sites essential for T cell lineage commitment at the level of chromatin.

genetics↗

Pollen sequencing reveals barriers and aberrant patterns of recombination in interspecific tomato hybrids

Tomato is the most consumed vegetable in the world. Increasing its natural resistance and resilience is key for ensuring food security within a changing climate. Plant breeders improve those traits by generating crosses of cultivated tomatoes with their wild relatives. Specific allele introgression relying on meiotic recombination, is hampered by structural divergence between parental genomes. However, previous studies of interspecific tomato hybridization focused in single cross or lacked resolution due to prohibitive sequencing costs of large segregating populations. Here, we used pooled-pollen sequencing to reveal unprecedented details of recombination patterns in five interspecific tomato hybrids. We detected hybrid-specific recombination coldspots that underscore the influence of structural divergence in shaping recombination landscape. Crossover regions and coldspots show strong association with specific TE superfamilies exhibiting differentially accessible chromatin between somatic and meiotic cells. We also found gene complexes associated with metabolic processes, stress resistance and domestication syndrome traits, revealing undesired consequences of recombination suppression to phenotypes. Finally, we demonstrate that by using resequencing data of wild and domesticated tomato populations, we can screen for alternative parental genomes to overcome recombination barriers. Overall, our results will allow breeders better informed decisions on generating disease-resistant and climate-resilient tomato.

genomics↗

Zbtb24 binding protects promoter activity by antagonizing DNA methylation in mESCs

DNA methylation is a key epigenetic modification essential for normal development. How particular factors control DNA methylation patterns and activity of a given locus is incompletely understood. The zinc finger protein Zbtb24 has been implicated in transcriptional activation/repression and the DNA methylation maintenance pathway. Here, using whole genome bisulfite sequencing in mouse embryonic stem cells, we report that besides a general trend towards DNA hypomethylation, many genomic sites gain methylation in the absence of Zbtb24 and they include promoters of actively transcribed genes. DNA hypomethylation is not generally associated with gene expression changes, suggesting that additional epigenetic safeguards are in place that ensure silencing of the affected loci. Remarkably, we identify a set of genes that is particularly susceptible to Zbtb24 occupancy. At these sites, Zbtb24 binding is not only required for gene activity but also required for maintaining the unmethylated state of the promoter.

molecular biology↗