HUMAN EMBRYONIC ZETA-GLOBIN GENE-EXPRESSION IN MOUSE-HUMAN HYBRID ERYTHROID CELL-LINES

The human alpha-globin-like embryonic zeta-globin chains are present i n abundance during the first 5 to 6 weeks of gestation. Subsequently, zeta-globin chains are present in fetal blood at a very low level, whi ch is supplanted by the expression of alpha-globin chains. Adult indiv iduals who are carriers of the (--(SEA)/) alpha-thalassemia deletion, in contrast to normal adults, have low levels of embryonic zeta-globin chains in their circulating erythrocytes. In this investigation, we c onstructed stable mouse-human hybrid cells with murine erythroleukemia cells bearing human chromosome 16, with either the normal alpha-globi n gene cluster (alpha alpha/) or the (--(SEA)/) type of alpha-thalasse mia deletion. The results on the human zeta-globin gene expression in these hybrid cells indicate that murine adult erythroid transcription factors can induce the expression of human embryonic zeta-globin gene in cis to the (--(SEA)/) deletion, in parallel with the endogenous mou se alpha-globin gene expression. These data also show the importance o f the DNA sequences within the (--(SEA)) deletion in regulating the ex pression of zeta-globin gene in cis during normal human hemoglobin ont ogeny. (C) 1995 by The American Society of Hematology.