Biological Sciences

Events and seminars

WT PhD Programme Seminar - The function of nuclear pore proteins in nuclear assembly and chromatin organisation

Peter Askjaer - Centro Andaluz de Biología del Desarrollo, Seville

2nd May 2018 at 12:00pm [Download iCalendar / .ics file]

Daniel Rutherford Building, G.27, Lecture Theatre 1

Nuclear pore complexes (NPCs) are fascinating molecular machines. They are essential regulators of nucleocytoplasmic transport, gene expression and genome stability and NPC components, the nucleoporins (NUPs), are involved in kinetochore assembly. 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 inactivation of MEL-28 in post-mitotic cells causes a dramatic lifespan reduction.

 

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/lamin and EMR-1/emerin 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, I will report behavioural data of mel-28 mutants, including developmental progression using a novel luciferase-based high-throughput method.

Host Eric Schirmer and Charles Dixon

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