Abstracts (complete list) - Wissenschaft Online

Jennifer Freyer, Stefan Floess, Alf Hamann, Jochen Huehn
REGULATION OF THE MURINE TRANSCRIPTION FACTOR
FOXP3
The transcription factor Foxp3 is specifically expressed in natural CD4+ regulatory T
cells and critically involved in their development and suppressive function. Although a
lot of knowledge has been accumulated regarding the function of Foxp3, relatively little
is known about the molecular regulation of Foxp3 expression. We have recently
identified an evolutionarily conserved region within the foxp3 locus upstream of the
translational start site, containing numerous CpG motifs, which in Tregs were selectively
demethylated compared to non-regulatory T cells. This conserved region, which we
named TSDR (Treg specific demethylated region), turned out to be associated with
acetylated and trimethylated histones specifically in Tregs, indicating an open chromatin
structure. Luciferase assays showed that the TSDR encompasses transcriptional activity,
which was affected by in vitro methylation. Currently, we are generating deletion
mutants of the TSDR to more precisely identify the critical elements involved in the
molecular control of Foxp3 expression.