Deletions within the mouse beta-globin locus control region preferentially reduce beta(min) globin gene expression.
The mouse beta-globin gene cluster is regulated, at least in part, by a locus control region (LCR) composed of several developmentally stable DNase I hypersensitive sites located upstream of the genes. In this report, we examine the level of expression of the beta(min) and beta(maj) genes in adult mice in which HS2, HS3, or HS5,6 has been either deleted or replaced by a selectable marker via homologous recombination in ES cells. Primer extension analysis of RNA extracted from circulating reticulocytes and HPLC analysis of globin chains from peripheral red blood cells revealed that all mutations that reduce the overall output of the locus preferentially decrease beta(min) expression over beta(maj). The implications of these findings for the mechanism by which the LCR controls expression of the beta(maj) and beta(min) promoters are discussed.
Alami
R
R
Division of Hematology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Bender
M A
MA
Feng
Y Q
YQ
Fiering
S N
SN
Hug
B A
BA
Ley
T J
TJ
Groudine
M
M
Bouhassira
E E
EE
D000818:Animals; D001483:Base Sequence; D002843:Chromatin / Q000648:ultrastructure; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D015672:Erythroid Precursor Cells / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D018390:Gene Targeting; D005838:Genotype; D005914:Globins / Q000096:biosynthesis / Q000235:genetics*; D019901:Locus Control Region / Q000235:genetics*; D008297:Male; D051379:Mice / Q000235:genetics*; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D017384:Sequence Deletion
D002843:Chromatin; D005914:Globins