The
delta-globin gene produces the delta chain of
Hb A2 which represents less than 3% of the
hemoglobin (Hb) in normal individuals. The
delta-globin gene is also expressed in the human
erythroleukemia cell line K562. The expression of the
delta-globin gene in this cell line is unexpected since K562 shows an embryonic-fetal
globin gene expression pattern with no expression of the adult
beta-globin gene.
delta-Globin gene activation has been proposed as a potential therapeutic tool for the cure of
delta-thalassemia (thal). In order to shed some light on the
delta-globin gene activation in K562 the present study has: (1) determined the complete nucleotide sequence of the delta- and
beta-globin genes; (2) assessed, by reverse transcription-polymerase chain reaction (RT-PCR), the relative delta- and
beta-globin mRNA level; and (3) analyzed the exact level of the endogenous expression
delta-globin gene by S1 mapping. No sequence variations were identified in the (delta- and
beta-globin genes when compared to the normal sequences.
delta-Globin mRNA represent more than 95% of the total delta + beta-
mRNA content. The level of expression of the
delta-globin gene is 12.3% (+/- 1.2) compared to the endogenous
alpha-globin gene. These results indicate that the high expression of the
delta-globin gene in K562 is most likely due to the transacting environment. Therefore, the presence and/or absence of specific transacting factors are able to specifically activate the human
delta-globin gene. The level of expression of the
delta-globin gene in this cell line suggests that it could be of relevance to identify the transacting factor(s) responsible for this selective activation in order to better understand the molecular mechanisms undergoing gene activation.