FKLF-2: a novel Krüppel-like transcriptional factor that activates globin and other erythroid lineage genes.
FKLF-2, a novel Krüppel-type zinc finger protein, was cloned from murine yolk sac. The deduced polypeptide sequence of 289 amino acids has 3 contiguous zinc fingers at the near carboxyl-terminal end, an amino-terminal domain characterized by its high content of alanine and proline residues and a carboxyl-terminal domain rich in serine residues. By Northern blot hybridization, the human homologue of FKLF-2 is expressed in the bone marrow and striated muscles and not in 12 other human tissues analyzed. FKLF-2 is constitutively expressed in established cell lines with an erythroid phenotype, but it is inconsistently expressed in cell lines with myeloid or lymphoid phenotypes. The expression of FKLF-2 messenger RNA (mRNA) is up-regulated after induction of mouse erythroleukemia cells. In luciferase assays, FKLF-2 activates predominantly the gamma, and to a lesser degree, the epsilon and beta globin gene promoters. The activation of gamma gene promoter does not depend on the presence of an HS2 enhancer. FKLF-2 activates the gamma promoter predominantly by interacting with the gamma CACCC box, and to a lesser degree through interaction with the TATA box or its surrounding DNA sequences. FKLF-2 also activated all the other erythroid specific promoters we tested (GATA-1, glycophorin B, ferrochelatase, porphobilinogen deaminase, and 5-aminolevulinate synthase). These results suggest that in addition to globin, FKLF-2 may be involved in activation of transcription of a wide range of genes in the cells of the erythroid lineage.
Asano
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Division of Medical Genetics, University of Washington, Seattle, WA 98195, USA.
Li
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XS
Stamatoyannopoulos
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G
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D003001:Cloning, Molecular; D015672:Erythroid Precursor Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics*; D018922:HL-60 Cells; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
D012333:RNA, Messenger; D014157:Transcription Factors; D005914:Globins