Blood, Vol. 95 No. 1 (January 1), 2000:
pp. 111-119
DNA methylation represses the expression of the human
erythropoietin gene by two different mechanisms
Hong Yin and
K. L. Blanchard
From the Feist-Weiller Cancer Center, Department of Medicine,
Louisiana State University Medical Center, Shreveport, LA.
The human erythropoietin gene is expressed predominantly in the
kidney and liver in response to hypoxia. Although the signaling cascade
for hypoxia is present in many different cell types, the expression of
erythropoietin is restricted to only a few tissues. The authors show
that the promoter and 5'-untranslated region (5'-UTR) of
the erythropoietin gene comprise a CpG island and that methylation of
the CpG island correlates inversely with expression. Methylation
represses the expression of the erythropoietin gene in 2 ways:
high-density methylation of the 5'-UTR recruits a methyl-CpG binding protein to the promoter, and methylation of CpGs in the proximal promoter blocks the association of nuclear proteins. (Blood.
2000;95:111-119)