Transcriptional Regulatory Elements Within the First Intron of Bruton's Tyrosine Kinase

摘要: Defects in the gene for Bruton's tyrosine kinase (Btk) result disorder X-linked agammaglobulinemia (XLA). Whereas XLA is characterized by a profound defect B-cell development, Btk expressed both B lymphocyte and myeloid cell lineages. We evaluated patient with who had reduced amounts of transcript but no abnormalities his coding sequence. A single base-pair substitution first intron was identified this patient, suggesting that region may contain regulatory elements. Using reporter constructs we two transcriptional control elements 500 bp 1. strong positive regulator, active pre-B cells cells, within 43 intron. Gel-shift assays Sp1 binding sites element. The patient's mutation results an altered specificity proximal site. negative only, located between base pairs 281 491 These findings indicate regulation transcription complex involve several factors at different stages differentiation.