|Kruppel-like factor 1 (erythroid)|
|Symbols||KLF1 (; EKLF; HBFQTL6; INLU)|
Krueppel-like factor 1 is a protein that in humans is encoded by the KLF1 gene. The gene for KLF1 is on the human chromosome 19 and on mouse chromosome 8. Krueppel-like factor 1 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.
KLF1 has been linked to three main processes that are all essential to transcription of the β globin gene:
- Chromatin remodeling
- Modulation of the gamma to beta globin switch
- Transcriptional activation
KLF1 binds specifically to the CACC motif of the β globin gene promoter. When natural mutations occur in the promoter, β+ thalassemia can arise in humans. Thalassemia's prevalence (2million worldwide carry the trait) makes KLF1 clinically significant.
KLF1 deficient (knockout) mouse embryos exhibit a lethal anemic phenotype, fail to promote the transcription of adult β globin, and die by embryonic day 1. On the other hand, over-expression of KLF1 results in a reduction of the number of circulating platelets and hastens the onset of β globin gene.
- Brown RC, Pattison S, van Ree J, Coghill E, Perkins A, Jane SM, Cunningham JM (January 2002). "Distinct domains of erythroid Krüppel-like factor modulate chromatin remodeling and transactivation at the endogenous beta-globin gene promoter". Mol. Cell. Biol. 22 (1): 161–70. PMC 134232. PMID 11739731.
- Perkins AC, Sharpe AH, Orkin SH (May 1995). "Lethal beta-thalassaemia in mice lacking the erythroid CACCC-transcription factor EKLF". Nature 375 (6529): 318–22. doi:10.1038/375318a0. PMID 7753195.
- Gardiner MR, Gongora MM, Grimmond SM, Perkins AC (2007). "A global role for zebrafish klf4 in embryonic erythropoiesis". Mech. Dev. 124 (9-10): 762–74. doi:10.1016/j.mod.2007.06.005. PMID 17709232.
- Tewari R, Gillemans N, Wijgerde M, Nuez B, von Lindern M, Grosveld F, Philipsen S (April 1998). "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". EMBO J. 17 (8): 2334–41. doi:10.1093/emboj/17.8.2334. PMC 1170576. PMID 9545245.
- 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