Characterization of murine BATF: a negative regulator of activator protein-1 activity in the thymus

BATF belongs to the AP-1/ATF superfamily of transcription factors and forms heterodimers with Jun proteins to bind AP-1 consensus DNA. Unlike Fos/Jun heterodimers which stimulate gene transcription, BATF/Jun heterodimers are transcriptionally inert and inhibit biological processes that are associate d with the overstimulation of AP-1 activity. Here, we describe the murine B ATF cDNA and genomic clones and map the BATF locus to chromosome 12 D2-3. U sing in situ hybridization of BATF mRNA, we show that BATF gene expression is highly restricted, with the most prominent signals detected in the thymu s. BATF mRNA levels are regulated differentially during discrete stages of T cell development and are up-regulated following activation of T cells in the periphery. To demonstrate the impact of BATF on AP-1 activity in vivo, AP-1 luciferase reporter mice were crossed to transgenic mice overexpressin g BATF exclusively in thymic T cells. Results show that elevated levels of BATF protein correlate with reduced transactivation by AP-I. Since the diff erential regulation of AP-1 activity is linked to key transitions in the de veloping immune system, our observations support a critical role for BATF i n determining the overall level of AP-1 activity, and thus AP-1 target gene expression, in specific T cell subtypes.