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Spatiotemporal control of gene expression to analyse nuclear organisation and beyond

AuthorsMuñoz-Jiménez, Celia; Ayuso, Cristina ; Dobrzynska, Agnieszka ; Macías-León, Javier; González-Aguilera, Cristina ; Torres-Méndez, Antonio; Cruz, Patricia de la; Askjaer, Peter
Issue Date28-Mar-2019
CitationVII Spanish Worm Meeting (2019)
AbstractThree-dimensional chromatin organisation has profound effects on gene expression and thereby also on a broad variety of processes, such as cell proliferation, differentiation and development. Furthermore, alterations in nuclear organisation can cause organismal dysfunction and shorten lifespan. We focus on the role of the nuclear envelope in chromatin organisation, and in particular on the inner nuclear membrane protein emerin, which when mutated in humans leads to Emery Dreifuss muscular dystrophy. To understand how lack of emerin, which is ubiquitously expressed, provokes tissue-specific symptoms, we have mapped the chromatin interaction profile of the C. elegans ortholog EMR-1 as well as LMN-1/lamin by DamID. Surprisingly, EMR-1 is enriched at neuronal genes and emr-1 mutants have abnormal neuromuscular junction signalling activity. During these studies, we developed a novel FLP/Frt-based toolkit to enable precise spatiotemporal control of gene expression. We used these tools to obtain, for the first time, data on nuclear organisation in specific tissues, including neurons, muscles and intestine within intact animals. However, the versatility of the toolkit goes beyond DamID and can be used to induce expression of genes (e.g. dominant negative mutants, toxin for cell ablation, etc.) in particular cell types at a given moment during development. The toolkit is also compatible with the GAL4-UAS system, which further enhances its utility. Finally, we are testing the possibility of using the toolkit to obtain gene expression profiles from specific tissues without the need to isolate individual cell types. We will present an overview of these tools and examples of what they have revealed about nuclear organisation.
DescriptionResumen del trabajo presentado en el VII Spanish Worm Meeting, celebrado en Barcelona (España), los días 28 y 29 de marzo de 2019
Appears in Collections:(CABD) Comunicaciones congresos
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