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...

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Bibliographic Details
Published in:European journal of immunology 2001-05, Vol.31 (5), p.1620-1627
Main Authors: Williams, Kristi L., Nanda, Indrajit, Lyons, Gary E., Kuo, Chay T., Schmid, Michael, Leiden, Jeffrey M., Kaplan, Mark H., Taparowsky, Elizabeth J.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
AP‐1
Base Sequence
Basic-Leucine Zipper Transcription Factors
BATF
BATF gene
BATF protein
Cell Differentiation
Cells, Cultured
chromosome 12
Cloning, Molecular
Gene Expression Regulation, Developmental
Genes, Reporter - genetics
In Situ Hybridization
In Situ Hybridization, Fluorescence
Lymphocyte
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Mice, Transgenic
Molecular Sequence Data
Organ Specificity
Physical Chromosome Mapping
RNA, Messenger - genetics
RNA, Messenger - metabolism
Spleen - cytology
Spleen - immunology
T-Lymphocytes - cytology
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Thymus Gland - cytology
Thymus Gland - immunology
Thymus Gland - metabolism
Transcription
Transcription Factor AP-1 - antagonists & inhibitors
Transcription Factor AP-1 - chemistry
Transcription Factor AP-1 - genetics
Transcription Factor AP-1 - metabolism
Transcription Factors - chemistry
Transcription Factors - genetics
Transcription Factors - metabolism
Transcriptional Activation
Transgenic mice
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Summary: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 inthymic 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.
ISSN:0014-2980
1521-4141
DOI:10.1002/1521-4141(200105)31:5<1620::AID-IMMU1620>3.0.CO;2-3