Transcriptional regulation of inflammatory genes

• Research unit: IRB
• Project number: 2000-GN-01

Key words (English)

Immmunology, Innate Immunity, Signal Transduction

Short description (English)

Macrophages and dendritic cells are highly differentiated and specialized cell types programmed to organize a complex response upon encounter with even very small concentrations of microbial products and inflammatory cytokines. The result of this response, which is collectively indicated as inflammation, is to contain the invading pathogen and kill it.

Project aims (English)

. The activity of the group is focused on the investigation of the mechanisms implicated in the transmission to the transcriptional apparatus of the signals generated at the surface of these cell types by contact with the microorganisms. The most challenging aspect of the ongoing projects is to define how highly specific and precisely tuned responses can be induced by different classes of stimuli. We are investigating how a fine modulation of the interplay between a relatively limited number of signal transducers and transcriptional activators can generate a potentially very high number of qualitatively different responses. In particular, we are trying to define the contribution of signal-induced modifications in chromatin structure at the level of individual genes to the generation of different degrees of transcriptional competence.

Abstract (English)

Based on accessibility of inflammatory cytokine and chemokine gene promoters to transcription factors required for efficient transcriptional activation, we have identified two classes of genes: those displaying constitutively accessible binding sites for essential transcription factors (such as NFkB) and those that have to be conformationally modified to allow for transcription factor recruitment. We have identified specific signals delivered to histone and to proteins implicated in the regulation of chromatin dynamics, that critically affect the ability of individual stimuli to switch on transcription of specific genes.