Disease relevance of Klf4

• Klf4 mutants also display aberrant expression of acidic mucins and TFF2/SP-positive cells, findings characteristic of premalignant conditions, but no inflammation, intestinal metaplasia, dysplasia, or cancer up to 1 year of age [1].
• Conditional deletion of the mouse Klf4 gene results in corneal epithelial fragility, stromal edema, and loss of conjunctival goblet cells [2].
• Kr??ppel-like factor 4 (Klf4), a gene down-regulated in activated murine B cells, is expressed at low levels in several types of human B-cell lineage lymphomas and leukemias [3].
• Klf4-deficient mice fail to establish the barrier function of the skin and die shortly after birth due to dehydration [4].

High impact information on Klf4

• Particularly interesting examples include modulation of the expression of transglutaminase 1 enzyme, the transcription factor Klf4 and the claudin tight junction proteins [5].
• Thus, Klf4 is critical for normal gastric epithelial homeostasis [1].
• Murine embryonic stem cell differentiation is promoted by SOCS-3 and inhibited by the zinc finger transcription factor Klf4 [6].
• Specifically, we generated lines of mice that express Klf4 from a tetracycline inducible promoter when crossed with transgenic mice expressing the tetracycline transactivator tTA from the epidermal keratin 5 promoter [7].
• However, Klf4(-/-) mice demonstrate a 90% decrease in the number of goblet cells in the colon, show abnormal expression of the goblet cell-specific marker Muc2 by in situ hybridization, have abnormal staining of the colonic epithelium with Alcian Blue for acidic mucins, and lack normal goblet cell morphology by ultrastructural analysis [8].

Biological context of Klf4

• Klf4(-/-) mice exhibit normal cell proliferation and cell death rates in the colon on postnatal day 1 [8].
• The mouse Krüppel-like Factor 4 (Klf4) gene: four functional polyadenylation sites which are used in a cell-specific manner as revealed by testicular transcript analysis and multiple processed pseudogenes [9].
• Finally, we document six Klf4 pseudogenes most likely formed by L1-mediated retrotransposition, indicating germ line expression of Klf4 [9].
• The transcription factor Krüppel-like factor 4 (Klf4) is involved in cell cycle arrest and terminal differentiation of many epithelial cell types [9].
• These findings support an important role for KLF4 as a regulator of key signaling pathways that control macrophage activation [10].

Anatomical context of Klf4

• Unlike Klf4, Klf5 mRNA is detected in the E15.5 meninges and in the E.16.5 epithelium of trachea and bronchi [11].
• Maximal Klf4 expression in the gastrointestinal tract is limited to a narrower window of time during the late phase of development [11].
• In summary, Klf4 plays a crucial role in colonic epithelial cell differentiation in vivo [8].
• We have recently shown that Northern blot analysis of RNA from adult mouse testis revealed multiple Klf4 transcripts [9].
• The importance of Klf4 in terminal differentiation of keratinocytes has been demonstrated by targeted gene ablation in mice [4].

Associations of Klf4 with chemical compounds

• The KLF4 induction of the iNOS promoter is mediated by two KLF DNA-binding sites at -95 and -212 bp, and mutation of these sites diminished induction by IFN-gamma and LPS [10].
• GKLF induction by H-Fe is mediated through hydroxyl radicals, p38MAP kinase-, calcium-, and protein synthesis-dependent pathways [12].

Regulatory relationships of Klf4

• Furthermore, GKLF was not highly expressed in differentiated SMCs in vivo, and TGF-beta down-regulated GKLF expression in dedifferentiated cultured SMCs [13].

Other interactions of Klf4

• Here, we examined the developmental expression of the mouse Klf5 gene and compared it to the established pattern of the Klf4 gene [11].
• We have used real-time PCR to confirm the changes in levels of transcripts such as renin-1, Kruppel-like factor 4, Mad4 (max-interacting protein repressor), Nur-related protein 1, and hairy/enhancer of splits gene 1 that were found to be regulated by FSH in testes of hpg mice [14].

References