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Transcriptional regulation and chromatin structure of the human CD34 gene
promoter region
XY He, PN Cockerill, D Cen and BR Davis
Geraldine Brush Cancer Research Institute, San Francisco, CA.
The human CD34 surface antigen is selectively expressed on stem/progenitor
cells within the hematopoietic system. Because CD34 expression is tightly
linked to the immature status of hematopoietic cells, with expression being
rapidly lost as hematopoietic cells mature and differentiate, an
examination of its regulation may provide important insights into the
molecular control of blood cell development. A comparison of the CD34
nuclear transcription rate in CD34+ and CD34- cells indicated that the CD34
gene is transcriptionally regulated in hematopoietic cell lines. In a
previous report, we had identified two major clusters of CD34 transcription
initiation sites by 5' RACE (rapid amplification of cDNA ends) analysis. In
transient transfection experiments, we now demonstrate the ability of
sequences encompassing each of these clusters to function as promoters of
transcription in CD34+ cells. These promoters functioned at equivalent
levels in CD34+ and CD34- cells, and the addition of 5' flanking sequences,
extending as far as 3.7 kb upstream, to the core promoters did not
differentially modify the level of expression in CD34+ versus the CD34-
cell lines. An examination of DNase I hypersensitivity sites within an
18-kb segment of DNA, extending 9 kb either side of the proximal promoter,
showed six sites that were primarily associated with CD34- expressing
cells. Taken together, these data indicate that the CD34 promoter sequences
alone do not confer tissue-or stage-specific expression. Appropriate
transcriptional regulation of the CD34 gene must be controlled by chromatin
structure, as identified by DNase I hypersensitivity, and/or by other
tissue- and stage-specific elements present outside of the promoter region.
Volume 83,
Issue 7,
pp. 1822-1830,
04/01/1994
Copyright © 1994 by The American Society of Hematology

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