Author:
FERNANDEZ DE LUCO HERNANDEZ REINA.
Year:
2006.
University:
BARCELONA [
www.ub.es].
Place of defense: FACULTAD DE BIOLOGÍA.
Place of preparation: UNIVERSIDAD DE BARCELONA (FACULTAD DE BIOLOGÍA).
Summary: Mutations in the transcription factor HNF1a are the most frequent cause of diabetes type MODY. The objective of this thesis is working to understand genetic models used functional aspects of HNF1a in a cell in vivo. Specifically, using a model expression of HNF1a conditional and specific beta cell, we show that the transcriptional activator function of this cell has autonomy in the beta cell, can be partially rescued in adulthood and is highly dependent on the levels of expression. We are also interested to see how exercises HNF1a function using a poor model for Hnf1a. We demonstrate that HNF1a not only induces locally histone modifications in chromatin their target genes, but also induces selective repositioning loci subdomains to the very rich histone modifications induced locally. For the first time, evidence that a gene activator can reset their target and that the histone modifications have a spatial representation in the nucleus. These resutlados have important implications for understanding the molecular basis of human disease and therefore in the design of future gene therapies.
