DNA methylation of remote sequences in chicken alpha-globin gene expression.

We have previously reported a correlation between site-specific DNA methylation and developmental expression of the chicken alpha-globin genes [8]. We have now extended this investigation to include sites 10-20 kb 5' to the alpha-globin cluster. These data indicate that the methylation status of DNA 5' to the globin genes can still be correlated with gene expression in red blood cells. The results suggest a possible role of DNA methylation in modifying regulatory sequences remote from the transcription initiation sites of globin genes; the existence of such remote regulatory sequences has also been indicated by some beta-thalassemia deletions and by genetic elements in other systems. Our results further correlate with known intermediate DNase I sensitivity in this region [7]. A discrete cluster of CpC type methylation is reported 5' to the alpha-globin gene cluster.