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Post-mitotic roles of MEL-28 in gene expression and lifespan regulation

AuthorsRomero Bueno, Raquel; Muñoz-Jiménez, Celia; Dobrzynska, Agnieszka CSIC ORCID CVN; Gómez-Saldívar, Georgina CSIC; Askjaer, Peter CSIC ORCID
Issue Date13-Jun-2018
CitationEMBO Workshop C. elegans development, cell biology and gene expression and European Worm Meeting (2018)
AbstractNucleoporins are the constituents of nuclear pore complexes (NPCs) and are essential regulators of nucleocytoplasmic transport, gene expression and genome stability. The nucleoporin MEL-28/ELYS plays a critical role in NPC assembly through recruitment of the NUP107-160 subcomplex, and is required for correct meiotic and mitotic chromosomes segregation. However, MEL-28 is also expressed in post-mitotic cells, suggesting that it might have additional functions. In support of this, we have observed that mel-28 mutants have a dramatically reduced lifespan, both in the presence of proliferating germ cells and in sterile glp-4 animals. We have mapped several functional domains in MEL-28, including a C-terminal DNA binding domain. Combined with the observation that a significant fraction of MEL-28 localises in the nucleoplasm, we speculate that MEL-28 might be directly involved in control of gene expression. To identify genes potentially regulated by MEL-28 we performed DamID experiments. This revealed that MEL-28¿s binding profile is different from those of others nuclear envelope proteins (NPP-22/NDC1, LMN-1/lamin and EMR-1/emerin), associating more frequently with chromosome centres. Interestingly, we found a positive correlation between MEL-28 peaks and active transcription markers, such as AMA-1/RNA pol II and methylated histone H3K4 and H3K36. In contrast, LMN-1 and EMR-1 are enriched outside MEL-28 associated domains (MADs). Moreover, expression levels of genes in MADs are higher than in MEL-28 gaps. MADs are enriched for genes involved in general cell biology processes but also larval development and locomotion. To analyse the functional relevance of MEL-28¿s association to chromatin, we are currently studying the effect of MEL-28 depletion on nuclear organization and gene expression. Finally, we will report behavioural data of mel-28 mutants, including developmental progression using a novel luciferase-based high-throughput method.
DescriptionResumen del póster presentado en EMBO Workshop C. elegans development, cell biology and gene expression and European Worm Meeting, celebrado en Barcelona (España) del 13 al 17 de junio de 2018.
Appears in Collections:(CABD) Comunicaciones congresos
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