Erythroid Krüppel-like factor (EKLF) is active in primitive and definitive erythroid cells and is required for the function of 5'HS3 of the beta-globin locus control region

The EMBO Journal
R TewariSjaak Philipsen

Abstract

Disruption of the gene for transcription factor EKLF (erythroid Krüppel-like factor) results in fatal anaemia caused by severely reduced expression of the adult beta-globin gene, while other erythroid-specific genes, including the embryonic epsilon- and fetal gamma-globin genes, are expressed normally. Thus, EKLF is thought to be a stage-specific factor acting through the CACC box in the beta-gene promoter, even though it is already present in embryonic red cells. Here, we show that a beta-globin gene linked directly to the locus control region (LCR) is expressed at embryonic stages, and that this is only modestly reduced in EKLF-/- embryos. Thus, embryonic beta-globin expression is not intrinsically dependent on EKLF. To investigate whether EKLF functions in the locus control region, we analysed the expression of LCR-driven lacZ reporters. This shows that EKLF is not required for reporter activation by the complete LCR. However, embryonic expression of reporters driven by 5'HS3 of the LCR requires EKLF. This suggests that EKLF interacts directly with the CACC motifs in 5'HS3 and demonstrates that EKLF is also a transcriptional activator in embryonic erythropoiesis. Finally, we show that overexpression of EKLF results in an ear...Continue Reading

References

Aug 1, 1991·Genes & Development·O HanscombeF Grosveld
Sep 1, 1995·Trends in Genetics : TIG·E Dzierzak, A Medvinsky
Mar 1, 1993·Baillière's Clinical Haematology·S L Thein
Mar 1, 1993·Baillière's Clinical Haematology·F GrosveldD Higgs
Jul 1, 1996·Developmental Dynamics : an Official Publication of the American Association of Anatomists·C M SouthwoodJ J Bieker
Oct 29, 1996·Proceedings of the National Academy of Sciences of the United States of America·A C PerkinsS H Orkin
Nov 15, 1996·Genes & Development·M WijgerdeP Fraser
Jul 11, 1998·Molecular Cell·N DillonF Grosveld

❮ Previous
Next ❯

Citations

Jul 24, 2002·Biochemical and Biophysical Research Communications·Weirong Xing, M Ram Sairam
Jul 4, 2002·Molecular Aspects of Medicine·Thomas Brittain
Mar 15, 2002·Current Opinion in Genetics & Development·Michael BulgerMark Groudine
Dec 3, 1999·The International Journal of Biochemistry & Cell Biology·T J SadlonB K May
Dec 3, 1999·The International Journal of Biochemistry & Cell Biology·A Perkins
Oct 17, 1998·The EMBO Journal·J GribnauP Fraser
Feb 13, 2003·Nucleic Acids Research·David A JacksonAnn Dean
Jun 29, 1999·Cold Spring Harbor Symposia on Quantitative Biology·R BaggaB M Emerson
Jan 24, 2007·Molecular and Cellular Biology·Yu-Chiau ShyuChe-Kun James Shen
Apr 5, 2001·Molecular and Cellular Biology·X Chen, J J Bieker
Jan 31, 2003·Molecular and Cellular Biology·Joëlle StarckFrançois Morle
Jun 1, 2005·Molecular and Cellular Biology·Roy DrissenSjaak Philipsen
Apr 16, 2005·Molecular and Cellular Biology·Akane OmoriKeiji Tanimoto
Dec 29, 2005·Blood·Denise HodgeAndrew Perkins
Aug 24, 2007·Blood·Pilar FronteloJames J Bieker
Oct 22, 2008·Molecular BioSystems·Adriana Miele, Job Dekker
Mar 11, 2008·Experimental Cell Research·Karen J QuadriniJames J Bieker
Feb 13, 2008·The FEBS Journal·Amel Haj KhelilFaouzi Baklouti
Mar 6, 2010·British Journal of Haematology·Vijay G SankaranStuart H Orkin
May 27, 2006·Experimental Hematology·Douglas G NilsonPatrick G Gallagher
May 27, 2011·Blood·Miroslawa Siatecka, James J Bieker
Nov 27, 1999·Blood Cells, Molecules & Diseases·M S RistaldiA Cao
Apr 26, 2005·Gene·Susanna PorcuMaria Serafina Ristaldi
Aug 3, 2010·Nature Genetics·Dewang ZhouTim M Townes
Nov 28, 2000·The Journal of Biological Chemistry·K PandyaT M Townes

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.