Beta-globin gene switching and DNase I sensitivity of the endogenous beta-globin locus in mice do not require the locus control region.
We have generated mice with a targeted deletion of the beta-globin locus control region (LCR). Mice homozygous for the deletion die early in embryogenesis but can be rescued with a YAC containing the human beta-globin locus. After germline passage, deletion of the LCR leads to a severe reduction in expression of all mouse beta-like globin genes, but no alteration in the developmental specificity of expression. Furthermore, a DNase I-sensitive "open" chromatin conformation of the locus is established and maintained. Thus, the dominant role of the LCR in the native locus is to confer high-level transcription, and elements elsewhere in the locus are sufficient to establish and maintain an open conformation and to confer developmentally regulated globin gene expression.
Bender
M A
MA
Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. mbender@fhcrc.org
Bulger
M
M
Close
J
J
Groudine
M
M
D000818:Animals; D002843:Chromatin / Q000648:ultrastructure*; D018244:Chromosomes, Artificial, Yeast; D018983:DNA Footprinting; D003850:Deoxyribonuclease I; D018507:Gene Expression Regulation, Developmental; D015321:Gene Rearrangement; D005914:Globins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D019901:Locus Control Region; D051379:Mice; D008817:Mice, Mutant Strains; D017384:Sequence Deletion; D013789:Thalassemia / Q000235:genetics
D002843:Chromatin; D005914:Globins; D003850:Deoxyribonuclease I