Transcriptional potentials of the beta-like globin genes at different developmental stages in transgenic mice and hemoglobin switching.

Developmental-stage-specific regulation and physiological levels of expression of the globin genes can be recaptured in transgenic mice carrying a YAC/BAC- or cosmid-based construct. By contrast, proper developmental regulation and high-level expression cannot be achieved coordinately in transgenic mice carrying a more manipulated construct, such as a plasmid-based globin gene construct. These differences provide us an opportunity to define the requirements for a developmentally regulated, high-level expression of the globin genes in vivo. To achieve this, as a first step, we studied maximum transcriptional potentials of the beta-globin genes at various stages of development. microLCR-enhanced expression of the epsilon-, gamma-, and beta-globin genes driven by their minimal promoters was estimated and compared with that in betaYAC transgenic mice. Quantitative measurements of steady state mRNA levels of the epsilon-, gamma-, and beta-globin genes showed that the microLCR was able to enhance expression of each beta-like globin gene to levels similar to those in the betaYAC mice. Moreover, transcriptional potentials of each globin gene were unchanged during the entire course of development. These observations indicate that the highest level of expression of the globin genes can be achieved in both embryonic and definitive erythropoiesis regardless of developmental specificity of the genes. This finding implies that transcription suppression is the major mechanism of the developmental specificity of the expression of the beta-like globin genes.