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Understanding gene regulation in nuclear space

Project description

Role of nuclear hotspots in the new gene expression paradigm

According to a new gene expression paradigm, genes and transcription factors cooperate to form specialised nuclear hotspots optimised for transcription. The EU-funded Hotspot project will investigate the hotspots that precede transcription during Zebrafish embryogenesis. The particular hotspots are large, isolated, long-lived, and their formation can be altered specifically. Initially, the research will determine the triggers of the hotspot formation, the components of hotspots and the order of the formation, followed by the study of the genes that come together. The researchers will develop an innovative method to visualise single-copy genes to reveal how stable gene expression programmes can emerge from the self-organising interactions between chromatin, transcription factors and the properties of transcribed sites.

Objective

There is accumulating evidence for a new gene expression paradigm, in which genes and transcription factors cooperate to create specialized nuclear hotspots optimized for transcription. How hotspots form, and how they impact transcription, however, is unclear. This is mostly because mechanistic and functional approaches have been limited by the large number of hotspots per nucleus, their small size, and their transient nature. Here, wThere is accumulating evidence for a new gene expression paradigm, in which genes and transcription factors cooperate to create specialized nuclear hotspots optimized for transcription. How hotspots form, and how they impact transcription, however, is unclear. This is mostly because mechanistic and functional approaches have been limited by the large number of hotspots per nucleus, their small size, and their transient nature. Here, we will take advantage of two hotspots that precede all other transcription during zebrafish embryogenesis. The hotspots are large, isolated, and relatively long-lived, and we can interfere with their formation specifically. They therefore provide an excellent opportunity to study nuclear hotspots. The stereotyped activation of transcription during embryogenesis further provides the opportunity to determine the effect of hotspots on gene expression. In Aim 1, we will determine what triggers hotspot formation, identify the components of hotspots and the order in which they come together, and determine the enrichment of components in hotspots compared to nucleoplasm. In Aim 2, we turn our attention to the genes that come together in these hotspots. We will develop a method to visualize single copy genes live and use this to determine how genes come together in transcription hotspots to be activated. Together, the work we propose will reveal how stable gene expression programs can emerge from the self- organizing interactions between chromatin, transcription factors and emergent properties of transcribed sites.

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Coordinator

UNIVERSITE DE LAUSANNE
Net EU contribution
€ 1 994 500,00
Address
Quartier unil-centre bâtiment unicentre
1015 Lausanne
Switzerland

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Region
Schweiz/Suisse/Svizzera Région lémanique Vaud
Activity type
Higher or Secondary Education Establishments
Links
Other funding
€ 0,00

Beneficiaries (1)