KLF1

Kruppel-like factor 1 (erythroid)
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2L2I​, 2MBH​
Identifiers
Symbols	KLF1 ; CDAN4; EKLF; HBFQTL6; INLU
External IDs	OMIM: 600599 HomoloGene: 4785 GeneCards: KLF1 Gene
Gene ontology Molecular function • core promoter proximal region sequence-specific DNA binding • transcription factor activity, sequence-specific DNA binding • transcription regulatory region DNA binding • metal ion binding Cellular component • nuclear chromatin • nucleus Biological process • transcription, DNA-templated • regulation of transcription, DNA-templated • erythrocyte differentiation • positive regulation of transcription, DNA-templated • cellular response to peptide Sources: Amigo / QuickGO
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: 12.88 – 12.89 Mb	Chr 8: 84.9 – 84.91 Mb
PubMed search

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

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

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 (2 million worldwide carry the trait) makes KLF1 clinically significant.

Clinical significance

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

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. doi:10.1128/mcb.22.1.161-170.2002. 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

• 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