The Structure and Regulation of the Human Carbonic Anhydrase I Gene
It has long been known that the genes coding for the closely related carbonic anhydrase (CA) I and II isozymes are tightly linked,19 and recent data from the analysis of somatic cell hybrids using cloned molecular probes have located not only CA I and CA II but also CA III to the long arm of chromosome 8.4,14 In collaboration with Yvonne Edwards’ group, we have used pulse-field electro-phoresis of large fragments of human DNA to show that the three genes lie within 200 kb of each other (unpublished data). Because these three genes have quite different patterns of tissue-specific expression (reviewed in reference 17), their proximity on chromosome 8 poses interesting questions concerning the molecular events responsible for differential gene activity. In the first instance, we need to define the organization of each gene and the characteristics of each transcription unit. The CA III gene, which is expressed in muscle and the liver of male rats, and the more generally expressed CA II gene have been cloned by groups in London12 and Ann Arbor,18 respectively; we have cloned the entire region containing the human CA I transcription unit, which is activated late in fetal development and expressed at high levels in erythroid tissues. It is now known that there is a second promoter within this transcription unit which is functional in colon in mice7 and humans (our unpublished data). Presented below is an outline of our current progress in identifying the different levels at which expression of the CA I gene is regulated in erythroid cells.
KeywordsCarbonic Anhydrase Globin Gene Erythroid Cell Transcription Unit Human Carbonic Anhydrase
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