Nucleic Acids Research, Vol 26, Issue 24 5684-5691, Copyright © 1998 by Oxford University Press
O Pomerantz, AJ Goodwin, T Joyce and CH Lowrey
Proper expression of the genes of the human beta-globin gene locus requires
the associated locus control region (LCR). Structurally, the LCR is defined
by the presence of four domains of erythroid-specific chromatin structure.
These domains, which have been characterized as DNase I hypersensitive
sites (HSs), comprise the active elements of the LCR. The major focus of
this research is to define the cis -acting elements which are required for
the formation of these domains of unique chromatin structure. Our previous
investigations on the formation of LCR HS4 demonstrated that NF-E2 and
tandem, inverted GATA binding sites are required for the formation of the
native HS. Similarly arranged NF-E2 and tandem GATA sites are present
within the core regions of the other human LCR HSs and are evolutionarily
conserved. Using site-directed mutagenesis of human HSs 2 and 3 we have
tested the hypothesis that these NF-E2 and GATA sites are common
requirements for the formation of all LCR HSs. We find that mutation of
these elements, and particularly the GATA elements, results in a decrease
or complete loss of DNase I hypersensitivity. These data imply the presence
of common structural elements within the core of each LCR HS which are
required for erythroid-specific chromatin structure reorganization.
ARTICLES
Conserved elements containing NF-E2 and tandem GATA binding sites are required for erythroid-specific chromatin structure reorganization within the human beta-globin locus control region
Department of Medicine and Department of Pharmacology/Toxicology, Dartmouth Medical School, Hanover, NH 03755, USA.
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