The gene defective in X-linked agammaglobulinemia (XLA) encodes a novel protein kinase termed Bruton's tyrosine kinase (Btk). Whereas the XLA phenotype is confined to abnormalities of B-cell development and function, Btk is expressed not only in B-lymphocyte lineage but also in myeloid lineage cells. The first 450 basepairs of the Btk promoter fused to a luciferase gene displayed a similar cell-type specificity. Critical binding sites for the transcription factors PU.1 and Sp1 were identified in the proximal portion of the Btk promoter upstream of a cluster of transcriptional start sites. Mutation of either the PU.1 or Sp1 site markedly reduced the activity of a Btk promoter-luciferase reporter construct in transfection experiments. In addition, PU.1 directly trans-activated the Btk promoter, and deletion of the PU.1 binding site abolished this effect. This study implicates PU.1 and Sp1 as major regulators of Btk expression and provides a foundation for further study of the regulation of this gene in XLA patients that lack Btk mRNA.
CITATION STYLE
Himmelmann, A., Thevenin, C., Harrison, K., & Kehrl, J. H. (1996). Analysis of the Bruton’s tyrosine kinase gene promoter reveals critical PU.1 and SP1 sites. Blood, 87(3), 1036–1044. https://doi.org/10.1182/blood.v87.3.1036.bloodjournal8731036
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