Objective
The Nuclear Factor kappa B (NF-kB) is a family of five structurally-related transcription factors that, in order to function, associate in homo- and hetero-dimeric form. Upon activation, NF-kB dimmers traslocate into the nucleus, bind to target sequences (k B sites) in the promoters of several genes, and activate transcription. The aim of this proposal is to elucidate the molecular mechanisms which confer specificity to NF-kB-dependent gene activation. In vitro studies have shown that the different NF-kB dimmers have almost the same ability to bind any given kB site. However, analyses of knock-out mice and cells have shown that each NF-kB dimmer regulates specific targets (although some genes respond redundantly to several NF-kB species). Since in most cell types multiple NF-kB subunits are co-expressed, with the resulting presence of a wide variety of dimmers at the same time, we will asses the contribution of each specific dimmer to determining a particular transcriptional phenotype. In the NF-kB system it i s possible to distinguish two kinds of specificity: one is at the promoter level, whereby different promoters within the same cell recruit distinct NF-kB dimmers. The second is cell type specificity, in which the same NF-kB-dependent gene behaves different ly in different cells. To investigate the molecular mechanisms underlying these phenomena, we will focus on differences in the chromatin structure of target promoters, and on co-factors which regulate NF-kB recruitment aand activity. We will systematically ly analyse histone modifications, and the activities of histone-modifying enzymes, at NF-kB-dependent gene promoters. In addition, we will isolate NF-kB-containing protein complexes from the nuclei of different cell types, and those directly bound to spec ific promoters. In this way, we will identify the differences between promoters and cells which result in distinct NF-kB transcriptional activity.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
You need to log in or register to use this function
Keywords
Call for proposal
FP6-2005-MOBILITY-8
See other projects for this call
Funding Scheme
EIF - Marie Curie actions-Intra-European FellowshipsCoordinator
MUNICH
Germany