High-resolution analysis of the human γ-globin gene promoter in K562 erythroleukemia cell chromatin

J. M. Gimble, E. E. Max, T. J. Ley

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2 Scopus citations

Abstract

We performed high-resolution mapping studies of the DNAse I-hypersensitive sites located just 5' to the human (G)γ- and (A)γ-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 the 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 γ-globin gene transcription about threefold. The region within the hypersensitive site includes all the consensus promoter elements of the γ-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).

Original languageEnglish
Pages (from-to)606-612
Number of pages7
JournalBlood
Volume72
Issue number2
DOIs
StatePublished - 1988

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