PMID: 9192642Jun 24, 1997Paper

A "knockdown" mutation created by cis-element gene targeting reveals the dependence of erythroid cell maturation on the level of transcription factor GATA-1

Proceedings of the National Academy of Sciences of the United States of America
M A McDevittS H Orkin

Abstract

The hematopoietic-restricted transcription factor GATA-1 is required for both mammalian erythroid cell and megakaryocyte differentiation. To define the mechanisms governing its transcriptional regulation, we replaced upstream sequences including a DNase I hypersensitive (HS) region with a neomycin-resistance cassette by homologous recombination in mouse embryonic stem cells and generated mice either harboring this mutation (neoDeltaHS) or lacking the selection cassette (DeltaneoDeltaHS). Studies of the consequences of these targeted mutations provide novel insights into GATA-1 function in erythroid cells. First, the neoDeltaHS mutation leads to a marked impairment in the rate or efficiency of erythroid cell maturation due to a modest (4- to 5-fold) decrease in GATA-1 expression. Hence, erythroid differentiation is dose-dependent with respect to GATA-1. Second, since expression of GATA-1 from the DeltaneoDeltaHS allele in erythroid cells is largely restored, transcription interference imposed by the introduced cassette must account for the "knockdown" effect of the mutation. Finally, despite the potency of the upstream sequences in conferring high-level, developmentally appropriate expression of transgenes in mice, other cis-reg...Continue Reading

References

Feb 1, 1991·Molecular and Cellular Biology·T Evans, G Felsenfeld
Apr 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·R HannonH Gould
Aug 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·T EvansG Felsenfeld
Oct 10, 1995·Proceedings of the National Academy of Sciences of the United States of America·H OsadaT H Rabbitts
Feb 1, 1995·Molecular and Cellular Biology·G A BlobelS H Orkin
Apr 1, 1993·Arteriosclerosis and Thrombosis : a Journal of Vascular Biology·S H GianturcoS M Grundy
Oct 29, 1996·Proceedings of the National Academy of Sciences of the United States of America·Y FujiwaraS H Orkin
Oct 1, 1996·Current Opinion in Genetics & Development·S H Orkin

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Citations

Sep 11, 1998·Developmental Dynamics : an Official Publication of the American Association of Anatomists·J Beckers, D Duboule
Oct 16, 2004·Pediatric Blood & Cancer·Yaddanapudi Ravindranath
Apr 1, 2010·Journal of Bone and Mineral Metabolism·Shuzo OkudairaTakashi Nakamura
Feb 11, 2005·Journal of Molecular Histology·Mary R Dusing, Dan A Wiginton
Oct 23, 2013·Current Hematologic Malignancy Reports·Niccolò BartalucciAlessandro M Vannucchi
Nov 26, 2003·Blood Cells, Molecules & Diseases·Marianne E GreeneJohn D Crispino
Aug 30, 2005·The American Journal of Pathology·Alessandro M VannucchiFrancesco Paoletti
Sep 5, 2001·Current Opinion in Genetics & Development·A B Cantor, S H Orkin
Dec 21, 2000·Trends in Cell Biology·A O'Garra, N Arai
Apr 20, 2010·Nature Genetics·Andrea AlimontiPier Paolo Pandolfi
Jun 15, 2011·The Journal of Biological Chemistry·Alexia EliadesKatya Ravid
May 5, 2012·The Journal of Biological Chemistry·Hiroshi KanekoRitsuko Shimizu
Feb 5, 2003·The Journal of Experimental Medicine·Anna Rita MigliaccioStuart H Orkin
May 12, 2010·The Journal of Experimental Medicine·Luyang YuWang Min
Feb 6, 2004·Current Opinion in Pediatrics·Amy E Geddis, Kenneth Kaushansky
Jun 10, 2006·Current Opinion in Rheumatology·Melissa A Kacena, Mark C Horowitz
Nov 3, 2007·Genes & Development·Osamu TanabeJames Douglas Engel
Mar 31, 2010·Molecular and Cellular Biology·Mariko TakayamaMasayuki Yamamoto
Dec 24, 2008·Molecular and Cellular Biology·Mikiko SuzukiMasayuki Yamamoto
Dec 2, 2004·Molecular and Cellular Biology·Ritsuko ShimizuMasayuki Yamamoto
Jul 19, 2005·Molecular and Cellular Biology·Mark A HallDavid J Curtis
Feb 3, 2005·Molecular and Cellular Biology·Rita FerreiraSjaak Philipsen
May 2, 2006·Molecular and Cellular Biology·Francesca BosèAntonella Ronchi
Jun 19, 2012·The Journal of Clinical Investigation·Vijay G SankaranHanna T Gazda

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