Group Mattias Mannervik

 

Differential regulation of gene expression in time and space controls cell fate, differentiation and development. The Drosophila embryo constitutes a particularly well characterized system in terms of both the cis-regulatory sequences driving gene expression and the trans-acting factors involved in controlling transcription. This knowledge can be exploited to study mechanisms for regulating transcription that are used in vivo, with important implications for both normal development and disease. Our work concerns the role of chromatin regulators in epigenetic inheritance, and the function of chromatin regulators and other proteins as transcriptional co-regulators.

 

Coregulators

In this project we identify and characterize transcriptional coregulators. Coregulators are proteins that themselves do not bind to DNA, but that facilitate communication between sequence-specific transcription factors and the basal RNA polymerase machinery. One function of coregulators is to modify the structure of chromatin, by acetylating (coactivators) or deacetylating (corepressors) histones.

Patterning

To find novel factors required for gene regulation in the Drosophila embryo, we have analyzed mutants isolated in a screen for maternal factors required for embryo patterning performed in the Nüsslein-Volhard laboratory in Tübingen (Luschnig et al. 2004). In my laboratory, we studied 15 mutants that cause segmentation defects and examined gene expression patterns in mutant embryos. We selected two mutants that produce specific gene expression phenotypes. These genes have been mapped, isolated and characterized molecularly. One mutant disrupts the brakeless gene. Brakeless is a nuclear protein of unknown function. In brakeless mutant embryos, we observed expanded expression domains of the gap genes Krüppel (Kr) and knirps (kni). We found that Tailless-mediated repression of kni expression is impaired in brakeless mutants. Tailless and Brakeless bind each other in vitro and interact genetically.

Epigenetics

Epigenetics can be defined as non-genetic changes that are transmitted through cell-divisions. The purpose of this project is to determine the function of chromatin modifying proteins in epigenetic inheritance during animal development. Chromatin modifications, such as histone acetylation and methylation may constitute an epigenetic code that influences the transcriptional state of the genome.

Mattias Mannervik, Professor

 

Visiting address:
Svante Arrhenius väg 20B
House E, room E331

Postal address:
The Wenner-Gren Institute
Developmental Biology
Stockholm University
S-106 91 Stockholm
 

Telephone: +46-8-16 1565
Fax: +46-8-612 6127
E-mail: mattias.mannervik@devbio.su.se