High-resolution analysis of the human gamma-globin gene promoter in K562 erythroleukemia cell chromatin.
We performed high-resolution mapping studies of the DNAse I-hypersensitive sites located just 5' to the human G gamma- and A gamma-globin genes of K562 erythroleukemia cells, in which these genes are constitutively expressed at low levels. This analysis revealed that the hypersensitive site extends from approximately -210 +/- 5 to -25 +/- 5 base pairs (bp) upstream from the transcription initiation site. Within this region, a GC-rich region located between the proximal CCAAT box and the TATA box is particularly accessible to nuclease digestion; however, the 5' end of the hypersensitive site is less accessible to nucleases. The pattern of DNAse I cleavage does not change on either strand with hemin induction of K562 cells, which increases the rate of gamma-globin gene transcription about threefold. The region within the hypersensitive site includes all the consensus promoter elements of the gamma-globin genes as well as an octamer sequence located between -182 and -175, and a region associated with a variety of mutations that may cause hereditary persistence of fetal hemoglobin (HPFH).
Gimble
J M
JM
Laboratory of Immunogenetics, NIAID, Bethesda, MD.
Max
E E
EE
Ley
T J
TJ
D002843:Chromatin / Q000032:analysis*; D002874:Chromosome Mapping; D004247:DNA / Q000032:analysis; D005914:Globins / Q000235:genetics*; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured
D002843:Chromatin; D012333:RNA, Messenger; D006427:Hemin; D005914:Globins; D004247:DNA