THE MECHANISM OF JUNB TRANSCRIPTIONAL REGULATION UNDER TLR ACTIVATION IN MOUSE MACROPHAGES

Abstract

Toll-like receptor (TLR) - pathway crosstalk caused by multiple PAMPs induces proinflammatory cytokine synergy in macrophages. Several potential synergistic factors including JunB have been found. But the mechanisms of junb regulation in macrophages are unclear. In this thesis work, we showed that junb mRNA and JunB protein were induced under single and combinatorial PAMP stimulations in macrophages. A junb downstream enhancer region significantly up-regulates junb transcription when cooperating with junb promoter. Mutagenesis analysis showed that four NF-?B sites in junb enhancer region are important for junb transcription. Furthermore, the junb promoter and enhancer co-pulldown assay followed by mass spectrometry analysis facilitated our identification of potential transcription factors including AATF, SSRP1 and TARDBP, which may regulate junb under different PAMP stimulations. Our findings delineate the functional regions in regulating junb and provide potential factors that may regulate junb under different PAMP stimulations.