Extensive methylation of a part of the CpG island located 3.0-4.5 kbp upstream to the chicken alpha-globin gene cluster may contribute to silencing the globin genes in non-erythroid cells
Sv. Razin et al., Extensive methylation of a part of the CpG island located 3.0-4.5 kbp upstream to the chicken alpha-globin gene cluster may contribute to silencing the globin genes in non-erythroid cells, J MOL BIOL, 299(4), 2000, pp. 845-852
Here, we show that in the chicken genome, the domain of alpha-globin genes
is preceded by a CpG island of which the downstream part (similar to 0.65 k
bp) is heavily methylated in lymphoid cells; it is either non-methylated or
undermethylated in erythroid cells. Recombinant plasmids were constructed
with the corresponding DNA fragment (called "uCpG") placed upstream to a re
porter CAT gene expressed from the promoter of the alpha(D) chicken globin
gene. Selective methylation of CpG dinucleotides within the uCpG fragment s
uppressed fivefold the expression of the CAT gene, when neither this gene i
tself nor the alpha(D) promoter were methylated. Methylation of CpG dinucle
otides within the aD gene promoter did not modify the suppression effect ex
erted by methylated uCpG. We interpret these results within the frame of th
e hypothesis postulating, that methylation of the upstream CpG island of th
e chicken alpha-globin gene domain may play an essential role in silencing
the alpha-globin genes in non-erythroid cells. (C) 2000 Academic Press.