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B-cell-specific demethylation of BTK, the defective gene in X-linked agammaglobulinemia

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Abstract

BTK, the gene that is defective in X-linked agammaglobulinemia, encodes a cytoplasmic tyrosine kinase that is critical for B-cell proliferation, or survival. To identify regulatory elements that control the expression of BTK we evaluated the methylation pattern of this gene in cell lines and in freshly isolated cells. An Hpa II site that was specifically demethylated in mature B cells but not in pre-B cells, T cells, neutrophils, or nonhematopoietic cells was identified in the tenth intron of BTK. In a 40 kilobase (kb) segment of DNA spanning the entire coding region of BTK plus 3 kb upstream of the first exon there were no other sites that demonstrated lineage-specific demethylation. The B-cell-specific demethylation site in intron 10, which falls within the SH2 domain, 26 kb distal to the first exon, occurs in a region rich in regulatory elements including two E2 boxes, two AP-2 sites, and a cAMP response element. It is likely that this site plays a role in maintaining BTK transcription in mature B cells.

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Author notes

  1. Ornella Parolini

    Present address: Clinica Pediatrica, Universita degli studi di Brescia, Presso Spedali Civili, 25123, Brescia, Italy

Authors and Affiliations

  1. Department of Immunology, St. Jude Children's Research Hospital, 332 N. Lauderdale, 38101, Memphis, TN, USA

    Ornella Parolini, Jurg Rohrer & Mary Ellen Conley

  2. Department of Experimental Oncology, St. Jude Children's Research Hospital, 332 N. Lauderdale, 38101, Memphis, TN, USA

    Linda H. Shapiro

  3. Department of Pediatrics, University of Tennessee College of Medicine, St. Jude Children's Research Hospital, 332 N. Lauderdale, 38101, Memphis, TN, USA

    Mary Ellen Conley

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  1. Ornella Parolini
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  2. Jurg Rohrer
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  3. Linda H. Shapiro
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  4. Mary Ellen Conley
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Additional information

The nucleotide sequence data reported in this Papershave been submitted to the Genbank nucleotide sequence and database have been assigned the accession number L31565

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Parolini, O., Rohrer, J., Shapiro, L.H. et al. B-cell-specific demethylation of BTK, the defective gene in X-linked agammaglobulinemia. Immunogenetics 42, 129–135 (1995). https://doi.org/10.1007/BF00178587

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  • DOI: https://doi.org/10.1007/BF00178587

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