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

Kristi L. Williams, Indrajit Nanda, Gary E. Lyons, Chay T. Kuo, Michael Schmid, Jeffrey M. Leiden, Mark H. Kaplan, Elizabeth J. Taparowsky

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

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 associated with the overstimulation of AP-1 activity. Here, we describe the murine BATF cDNA and genomic clones and map the BATF locus to chromosome 12 D2-3. Using in situ hybridization of BATF mRNA, we show that BATF gene expression is highly restricted, with the most prominent signals detected in the thymus. 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 overexpressing BATF exclusively in thymic T cells. Results show that elevated levels of BATF protein correlate with reduced transactivation by AP-1. Since the differential regulation of AP-1 activity is linked to key transitions in the developing immune system, our observations support a critical role for BATF in determining the overall level of AP-1 activity, and thus AP-1 target gene expression, in specific T cell subtypes.

Original languageEnglish (US)
Pages (from-to)1620-1627
Number of pages8
JournalEuropean Journal of Immunology
Volume31
Issue number5
DOIs
StatePublished - May 30 2001

Keywords

  • AP-1
  • BATF
  • Lymphocyte
  • Transcription
  • Transgenic mice

ASJC Scopus subject areas

  • Immunology

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