INHIBITION OF GENE-EXPRESSION BY THE (G)GAMMA 5'-FLANKING REGION OF THE BANTU BETA(S) CHROMOSOME

beta(s)-chromosome haplotypes are peculiar to specific regions of Afri ca and Asia and are associated with the occurrence of different fetal hemoglobin (Hb) levels in sickle cell patients. Among these haplotypes , Ps-chromosomes found in the Senegal and the Arab-India regions are a ssociated with relatively high levels of HbF expression, whereas those around the Benin, Bantu, and the Cameroon regions show low levels of HbF expression. The roles of 5'HS2 and the 5' flanking (promoter regio n) region in the expression of globin genes are well documented. Haplo type specific variations are found in these regions and have been post ulated to be involved in the regulation of HbF expression. In this stu dy, we have analyzed the effect of sequence variations in regulatory r egions of the Bantu 5'HS2 and 5' flanking region of the Gy gene on CAT expression. A diminution was observed in K562 cells when the promoter originated from the Bantu PS chromosome. The decreased expression was independent of the origin of the 5'HS2 sequence-combinations of the B antu promoter were measured with the Benin, Bantu, or Senegal 5'HS2 se quences in K562 cells. However, expression of the same plasmids in mur ine erythroleukemic (MEL) cells showed no difference in CAT expression among the various sequence combinations studied. (C) 1998 Wiley-Liss, Inc.