A single beta-globin locus control region element (5' hypersensitive site 2) is sufficient for developmental regulation of human globin genes in transgenic mice.
The beta-globin gene complex is regulated by an upstream locus control region (LCR) which is responsible for high-level, position-independent, erythroid-cell-specific expression of the genes in the cluster. Its role in the developmental regulation of beta-like globin gene transcription remains to be established. We have examined the effect of a single LCR element, hypersensitive site 2 (HS2), on the developmental regulation of the human fetal gamma and adult beta genes in transgenic mice. In mice bearing HS2A gamma beta and HS2G gamma A gamma-117 delta beta human globin gene constructs, switching from gamma- to beta-gene expression begins at about day 13.5 of gestation and is largely completed shortly after birth. The larger construct also demonstrates a switch in G gamma- to A gamma-gene expression during the gamma-to-beta switch similar to that observed during normal human development. We conclude that HS2 alone is sufficient for developmental regulation of the human beta-globin genes.
Morley
B J
BJ
MRC Molecular Haematology Unit, University of Oxford, John Radcliffe Hospital, England.
Abbott
C A
CA
Sharpe
J A
JA
Lida
J
J
Chan-Thomas
P S
PS
Wood
W G
WG
D000375:Aging; D000818:Animals; D003433:Crosses, Genetic; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005786:Gene Expression Regulation; D005809:Genes, Regulator; D005865:Gestational Age; D005914:Globins / Q000235:genetics*; D006454:Hemoglobins / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D005810:Multigene Family; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D015183:Restriction Mapping; D014158:Transcription, Genetic
D006454:Hemoglobins; D012333:RNA, Messenger; D012313:RNA; D005914:Globins; D004247:DNA