Cell type-specific transcriptional regulation of the human adenosine deaminase gene

The relative rates of transcription of the human adenosine deaminase (ADA) gene were determined in isolated nuclei from T and B lymphoblasts and skin fibroblasts. ADA gene transcription occurs at higher rates in T cells than in B cells and fibroblasts. Relative steady state ADA mRNA levels were also determined for each cell line, and these values were found to correlate with relative rates of transcription of the gene. Therefore, the primary mechanism for control of expression of this ubiquitous enzyme is at the level of transcription. The ratios of ADA enzymatic activity to specific mRNA content were also compared between cell lines. The B lymphoblasts exhibited lower ratios than did the T lymphoblasts, suggesting that rates of protein degradation were several fold greater in B than in T lymphoblast cell lines. This finding is consistent with previous direct measurements of ADA protein turnover. Differential rates of protein turnover in B as compared to T cells provide a secondary mechanism for the regulation of ADA expression. In addition to transcription initiation being the major control mechanism of steady state ADA mRNA in all cell lines, first intron elongation pausing occurs in fibroblasts, and discrete regions of RNA polymerase II and RNA polymerase III antisense transcripts are observed in all cell lines studied.