EKLF
Encyclopedia
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.
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
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
Thalassemia
Thalassemia is an inherited autosomal recessive blood disease that originated in the Mediterranean region. In thalassemia the genetic defect, which could be either mutation or deletion, results in reduced rate of synthesis or no synthesis of one of the globin chains that make up hemoglobin...
can arise in humans. Thalassemia's prevalence (2million worldwide carry the trait) makes EKLF clinically significant.