In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 97, No. 26 ( 2000-12-19), p. 14554-14559
Abstract:
Developmental expression at the β-globin locus is regulated
in part by the locus control region, a region upstream of the genes containing at least five major DNase I hypersensitive sites (HSs) in
mammalian erythrocytes. Sequences farther 5′ of these HSs are conserved in mouse and human, and both loci are embedded within a cluster of
functional odorant receptor genes. In humans, distant upstream sequences have been implicated in regulation of the β-globin genes.
In this study, the role of the 5′-most HSs and their adjacent sequence was investigated by deletion of an 11-kb region from the mouse locus,
including 5′HS 4.2, 5′HS 5, 5′HS 6, and the 5′β1 odorant receptor gene. Mice that were homozygous for this deletion were fully viable,
and no significant effect on adult β-globin gene expression was seen. 5′HSs 1–4, which are located downstream of the deletion, were still
present in the mutant mice. In addition, two new upstream HSs, HS −60.7 and HS −62.5, were found in erythroid tissue of both wild-type
and mutant mice. Therefore, although the possibility of a minor role still exists, neither the HSs nor the other regions deleted in this
study are essential for β-globin gene expression, and it is unlikely that chromatin structure is affected either upstream or downstream of
the deletion. This is the largest deletion at the mouse locus control region to show no apparent phenotype, and focuses attention on the
possible contribution of sequences even farther upstream.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.97.26.14554
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2000
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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