EKLF

Erythroid Krüppel-like Factor (EKLF) is a transcription factor that is necessary for the proper maturation of erythroid (red blood) cells. The molecule has two domains; the transactivation domain and the chromatin-remodeling domain. The carboxyl (C) terminal is composed of three C2H2 zinc fingers that binds to DNA, and the amino (N) terminus is proline rich and acidic [1]. The gene for EKLF is on the human chromosome 19 and on mouse chromosome 8.

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EKLF deficient (knockout) mouse embryos exhibit a lethal anemic phenotype, fail to promote the transcription of adult β globin, and die by embryonic day 14 [3]. On the other hand, over-expression of EKLF results in a reduction of the number of circulating platelets and hastens the onset of β globin gene [5].

EKLF has been linked to three main processes that are all essential to transcription of the β globin gene:

1.Chromatin remodeling

2.Modulation of the gamma to beta globin switch

3.Transcriptional activation

EKLF binds specifically to the CACC motif of the β globin gene promoter [4]. When natural mutations occur in the promoter, β+ thalassemia can arise in humans. Thalassemia's prevalence (2million worldwide carry the trait) makes EKLF clinically significant.

References

1. Brown R, Pattison S, van Ree J, Coghill E, Perkins A, Jane S, Cunningham J. Distinct Domains of Erythroid Krüppel-Like Factor Modulate Chromatin Remodeling and Transactivation at the Endogenous β-Globin Gene Promoter. Mol. Cell Biol. 22:7306, 2002.

2. Cooley's Anemia Foundation. About Thalassemia [Internet]. New York, NY: Cooley's Anemia Foundation National Office; 2001 [1 August 2007] . Available from: http://cooleysanemia.org/sections.php?sec=1&tab=8.

3. Hodge D, Coghill E, Keys J, Maguire T, Hartmann B, McDowall A, Weiss M, Grimmond S, Perkins A. A global role for EKLF in definitive and primitive erythropoesis. Blood. 2006 15 April 2006;107(8):3359-70.

4. Perkins A, Sharpe A, Orkin S. Lethal beta-thalassaemia in mice lacking the erythroid CACCC-transcription factor EKLF. Nature. 375:318, 1995.

5. Tewari R, Gillemans N, Wijgerde M, Nuez B, von Lindern M, Grosveld F, Philipsen S. Erythroid Ekuppel-like Factor is active in primitive and deifinitve erythroidd cells and is required for the function of 5' HS3 of the β globin locus control region. EMBO J. 17:2334, 1998.