Nucleic Acids Research, Vol 27, Issue 15 3130-3137, Copyright © 1999 by Oxford University Press
K Tanimoto, Q Liu, J Bungert and JD Engel
The polyoma virus enhancer (PyE) is capable of conferring integration
position-independent expression to linked genes in stably transfected
erythroid cells after joining to DNase I hypersensitive site (HS) 5 of the
human beta-globin locus control region (LCR). In attempting to separate the
chromatin opening activity of the LCR from its enhancer activity and to
investigate contributions of the individual HS core elements to LCR
function, the human beta-globin LCR HS2, HS3 and HS4 core elements were
replaced with the PyE within the context of a yeast artificial chromosome
(YAC) bearing the whole locus. We show here that, in contrast to its
function in cultured cells, the PyE is unable to replace HS core element
function in vivo. We found that the PyE substitution mutant LCR is unable
to provide either chromatin opening or transcriptional potentiating
activity at any erythroid developmental stage in transgenic mice. These
data provide direct evidence that the human beta-globin LCR core elements
specify unique functions that cannot be replaced by a ubiquitous enhancer
activity.
ARTICLES
The polyoma virus enhancer cannot substitute for DNase I core hypersensitive sites 2-4 in the human beta-globin LCR
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208-3500, USA.
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