Characterization of nuclear IL-1-regulated protein complexes that mediate chemokine gene expression
Michael Kracht is investigating how nuclear chromatin-associated factors mediate IL-1 regulated gene expression. IL-1 is a potent pro-inflammatory cytokine which is produced in tumors by tumor cells themselves but also by cells from the tumor microenvironment.
Depending on the context, IL-1 can have either tumor-promoting or -suppressing effects which are largely mediated by rapid induction or repression of hundreds of genes. Many of these genes are NF-kB and AP-1 dependent and can collectively support several major hallmarks of cancer as shown here on the right.
Strong expression of IL-1-induced genes requires incompletely understood cooperative effects of the transcription factors c-Jun and p65 NF-kB with chromatin-modifying enzymes.
A major goal is to gain deeper insight into the underlying mechanisms of this cooperativity at the level of chromatin. Thereby, the group will focus on identification of chromatin-associated transcriptional regulators, their cofactors and their posttranslational modifications that determine positive and negative roles of HDAC3 in transcription of a number of IL-1-induced co-regulated chemokine genes.