Sheltering of gamma-globin expression from position effects requires both an upstream locus control region and a regulatory element 3' to the A gamma-globin gene.

Molecular and Cellular Biology
J A StamatoyannopoulosQ Li

Abstract

Integration position-independent expression of human globin transgenes in transgenic mice requires the presence of regulatory elements from the beta-globin locus control region (LCR) in the transgene construct. However, several recent studies have suggested that, while clearly necessary, such elements are not by themselves sufficient to realize this effect. In the case of the human fetal gamma-globin genes, previous results have indicated that additional regulatory information required for sheltering of gamma-globin transgene expression from position effects may reside downstream from the A gamma gene. To investigate this possibility, we established 17 lines of transgenic mice carrying constructs comprising a micro-LCR (microLCR) element, an A gamma-globin gene fragment, and a variable length of 3' sequence information beyond the A gamma 3' HindIII site. gamma-Globin expression during development was studied in 170 individual F2 progeny from these lines. We find that gamma-globin expression becomes sheltered from position effects when the normally position-sensitive microLCR-A gamma construct is extended by 600 bp beyond the 3' HindIII site to include a previously identified regulatory sequence (the A gamma-globin enhancer), th...Continue Reading

References

Apr 1, 1992·Molecular and Cellular Biology·J A LloydJ B Lingrel
Jul 1, 1990·Trends in Genetics : TIG·T M Townes, R R Behringer
Sep 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·T EnverG Stamatoyannopoulos
Jul 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·W C ForresterM Groudine
Jul 15, 1995·European Journal of Biochemistry·S H Orkin
Nov 1, 1993·Molecular and Cellular Biology·I S ThoreyR G Oshima
Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·G RobertsonE Whitelaw
Feb 27, 1993·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·F GrosveldA Imam
Dec 1, 1993·Molecular and Cellular Biology·G StamatoyannopoulosQ Li
Jul 1, 1993·Molecular and Cellular Biology·M ReitmanG Felsenfeld
Apr 1, 1993·Trends in Genetics : TIG·N Dillon, F Grosveld
Mar 1, 1996·Nature Genetics·M A BedellN G Copeland
Apr 1, 1996·Trends in Genetics : TIG·E MilotF Grosveld

❮ Previous
Next ❯

Citations

Jul 12, 2005·Peptides·Francois Rouzaud, Vincent J Hearing
Aug 26, 1998·Proceedings of the National Academy of Sciences of the United States of America·Q LiuJ D Engel
Jul 22, 1997·Proceedings of the National Academy of Sciences of the United States of America·M A McDevittS H Orkin
May 1, 1999·Human Gene Therapy·D W EmeryG Stamatoyannopoulos
Jul 21, 1998·Annals of the New York Academy of Sciences·Q LiG Stamatoyannopoulos
Aug 5, 1998·Current Opinion in Genetics & Development·R A Swank, G Stamatoyannopoulos

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.