The architecture of gene regulation in development and disease
Event details
| Date | 11.11.2013 |
| Hour | 14:00 › 15:00 |
| Speaker |
Dr François Spitz Developmental Biology Unit EMBL Heidelberg Germany |
| Location | |
| Category | Conferences - Seminars |
The expression of vertebrate genes is regulated by cis-acting elements that can be hundreds of kilobases away from their promoter regions. The importance of these remote regulatory influences is exemplified by developmental malformations caused by their mutations. Results from genome-wide association studies suggest further that polymorphisms associated with remote regulatory elements modulate the incidence of common diseases in humans. Thus, the mechanisms that control the interactions between remote elements and the surrounding genes form an essential, yet poorly understood, step in the transformation of genomic information into gene expression programs.
To get insights into the principles and mechanisms that organise these cis-regulatory interactions networks, we have developed an in vivo chromosomal tagging and recombineering system. The analysis of the distribution of regulatory activities along mouse chromosomes showed that enhancers act pervasively across large domains, which overlap with the 3D conformation of the corresponding loci. We have engineered large series of chromosomal rearrangements to alter the normal linear distribution of genes, regulatory elements and domain boundaries at several model loci, and investigated how regulatory and physical interactions are impacted by changes in distances or relative order. As an example, I will present how our in vivo investigations of the 8q24 locus surrounding the Myc proto-oncogene in the mouse identify new remote enhancers controlling tissue-specific expression of Myc (during face morphogenesis and in hematopoietic stem cells), provide ways to move from association studies to biological functions, and reveal the role of specific features in the organisation of the regulatory architecture of this complex locus.
To get insights into the principles and mechanisms that organise these cis-regulatory interactions networks, we have developed an in vivo chromosomal tagging and recombineering system. The analysis of the distribution of regulatory activities along mouse chromosomes showed that enhancers act pervasively across large domains, which overlap with the 3D conformation of the corresponding loci. We have engineered large series of chromosomal rearrangements to alter the normal linear distribution of genes, regulatory elements and domain boundaries at several model loci, and investigated how regulatory and physical interactions are impacted by changes in distances or relative order. As an example, I will present how our in vivo investigations of the 8q24 locus surrounding the Myc proto-oncogene in the mouse identify new remote enhancers controlling tissue-specific expression of Myc (during face morphogenesis and in hematopoietic stem cells), provide ways to move from association studies to biological functions, and reveal the role of specific features in the organisation of the regulatory architecture of this complex locus.
Practical information
- Informed public
- Free
Organizer
- Prof. Denis Duboule
Contact
- Doris Sapin, SV-UPDUB, 37242