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The role of Barrier to Autointegration Factor in chromatin organisation and premature ageing

AuthorsRomero Bueno, Raquel; Gómez-Saldívar, Georgina ; Dobrzynska, Agnieszka ; Rojas, Marta; Ayuso, Cristina ; Riedel, Christian; Askjaer, Peter
Issue Date23-Oct-2019
CitationEuropean Developmental Biology Congress (2019)
AbstractBarrier to Autointegration Factor (BAF) is a highly conserved metazoan chromatin binding protein implicated in nuclear envelope (NE) breakdown and reassembly during mitosis as well as chromatin compaction. The localisation of BAF to the NE is interdependent of nuclear lamins and LEM-domain inner nuclear membrane proteins (LAP2, emerin, and MAN1). BAF is ubiquitously expressed and depletion of BAF causes early embryonic arrest. Strikingly, a single amino acid substitution in human BAF (Ala12Thr) causes Nestor-Guillermo Progeria Syndrome (NGPS), which affects a variety of tissues and leads to severe skeletal defects and scoliosis. It is intriguing why a mutation in an essential protein expressed throughout development triggers the development of symptoms only a few years into childhood. To explore Caenorhabditis elegans as model for this devastating disease, we have modified the baf-1 locus to mimic the human NGPS mutation (baf-1(G12T)). We found that baf-1(G12T) mutants are hypersensitive to NE perturbations, particularly to modifications in the nuclear lamina. This dramatically affects mitotic chromosome segregation and embryonic viability. Using Bimolecular Fluorescence Complementation, we discovered the nuclear pore and chromatin binding protein MEL-28/ELYS as a novel BAF interaction partner. In proliferating cells, MEL-28 is required for nuclear pore complex assembly, whereas we found that MEL-28 associates with active chromatin in post-mitotic cells. We are currently investigating the role of the NGPS mutation on BAF¿s interactions with MEL-28 and other NE proteins as well as BAF¿s function in chromatin organisation through DamID. We propose that changes in tissue-specific genome organisation are driving forces in disease development.
DescriptionTrabajo presentado en el European Developmental Biology Congress, celebrado en Alicante (España), del 23 al 26 de octubre de 2019
Appears in Collections:(CABD) Comunicaciones congresos
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