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Blood, 1 January 2002, Vol. 99, No. 1, pp. 348-356
RED CELLS
DNA-dependent adenosine triphosphatase (helicaselike
transcription factor) activates  -globin transcription in K562
cells
Milind C. Mahajan and
Sherman M. Weissman
From the Department of Genetics, Boyer Center for
Molecular Medicine, Yale University School of Medicine, New Haven, CT.
Correct developmental regulation of  -like globin gene expression
is achieved by preferential transcription of a gene at a given
developmental stage, silencing of other -like gene promoters, and
competition among these promoters for interaction with the locus
control region (LCR). Several evolutionarily conserved DNA elements in
the promoters of the -like genes and LCR have been studied in
detail, and the role of their binding factors has been investigated.
However, the -globin promoter includes additional evolutionarily
conserved sequences of unknown function. The present study examined the
properties of a 21-base pair (bp) promoter-conserved sequence (PCS)
located at positions  115 to 136 bp relative to the transcription
start site of the -globin gene. A helicaselike transcription factor
(HLTF) belonging to the SWI2/SNF2 family of proteins binds to the PCS
and a partly homologous sequence in the enhancer region of the LCR
hypersensitive site 2 (HS2). Elevation of the level of HLTF in K562
erythroleukemic cells increases -promoter activity in transient
transfection experiments, and mutations in the PCS that remove
HLTF-binding regions abolish this effect, suggesting that HLTF is an
activator of -globin transcription. Overexpression of HLTF in K562
cells does not affect the endogenous levels of  - and  -globin
message, but it markedly activates -globin transcription. In
conclusion, this study reports a transcription factor belonging to the
SWI2/SNF2 family, which preferentially activates chromosomal -globin
gene transcription and which has not previously been implicated in
globin gene regulation.
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