EKLF

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Erythroid Krüppel-like Factor
Identifiers
Symbol	EKLF
Alt. Symbols	KLF1
Entrez	10661
HUGO	6345
OMIM	600599
RefSeq	NM_006563
UniProt	Q13351
Other data
Locus	Chr. 19 p13.13-13.12

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.

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.

[edit] 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.