KLF1

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Kruppel-like factor 1 (erythroid)
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols KLF1 ; EKLF; HBFQTL6; INLU
External IDs OMIM600599 HomoloGene4785 GeneCards: KLF1 Gene
Orthologs
Species Human Mouse
Entrez 10661 16596
Ensembl ENSG00000105610 ENSMUSG00000054191
UniProt Q13351 n/a
RefSeq (mRNA) NM_006563 NM_010635
RefSeq (protein) NP_006554 NP_034765
Location (UCSC) Chr 19:
13 – 13 Mb
Chr 8:
84.9 – 84.91 Mb
PubMed search [1] [2]

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.

Structure[edit]

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]

Function[edit]

KLF1 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

KLF1 binds specifically to the CACC motif of the β globin gene promoter.[2] 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.

Clinical significance[edit]

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.[3] 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.[4]

References[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 

External links[edit]