Disease relevance of KLF9

• Forced expression of BTEB1, either by stable or transient transfections of BTEB1 expression constructs in endometrial carcinoma cells, enhanced SLPI promoter activity [1].
• BTEB is a GC-box binding transcription factor that can activate human immunodeficiency virus type 1 long terminal repeat and cellular gene promoters containing multiple GC boxes [2].
• The present studies showed that although BTEB mRNA was expressed in various tissues of mammals and cell lines, the expression of BTEB protein was confined to the brain and a neuroblastoma Neuro2A (N2A), suggesting that the BTEB expression was translationally regulated in a cell-specific or tissue-specific manner [2].
• An electrophoretic mobility shift assay demonstrated specific binding of BTEB to GC boxes of the HIV-1 LTR [3].
• Further, we provide support for the potential significance of the selective functional interactions of PR isoforms with BTEB1 in the peri-implantation uterus using mouse and pig models and in the breast cancer cell lines MCF-7 and T47D [4].

High impact information on KLF9

• We analyzed the promoter region of the dominant transcript (L2) of the murine GHR to determine that a cis element, L2C1, interacts with transcription factors NF-Y, BTEB1, and HMG-Y/I [5].
• Selective interactions of Kruppel-like factor 9/basic transcription element-binding protein with progesterone receptor isoforms A and B determine transcriptional activity of progesterone-responsive genes in endometrial epithelial cells [4].
• The Sp/KLF transcription factor basic transcription element-binding protein (BTEB1) regulates gene transcription by binding to GC-rich sequence motifs present in the promoters of numerous tissue-specific as well as housekeeping genes [4].
• To examine whether the 5'-UTR controlled the translation in a cell-specific manner, a fusion plasmid composed of the BTEB 5'-UTR and the chloramphenicol acetyltransferase gene was transfected into HeLa and N2A cells [2].
• Mutation of the GC box resulted in a loss of protein-binding activity, implicating involvement of a GC box-binding protein in the DNA/protein interaction [6].

Chemical compound and disease context of KLF9

• These results indicate that a panel of MAbs consisting of anti-keratin, anti-vimentin, NKI/C3 and NKI/Bteb is useful for a more accurate diagnosis of malignant melanomas on cytologic preparations [7].

Biological context of KLF9

• PR-B, rather than PR-A isoform, preferentially associated with BTEB1 in the GC-rich region, whereas both PR isoforms were recruited to the progesterone-responsive element-like site along with BTEB1 [1].
• A BTEB expression vector (pcDNA-3BTEB) was used to examine the effect of increased BTEB protein on UF gene expression and promoter activity in primary cultures of pig endometrial GE cells [8].
• A role for BTEB1 in the regulation of cell growth and gene transcription has been invoked, but little is known about the molecular mechanisms underlying these activities [9].
• Increased expression of the Zn-finger transcription factor BTEB1 in human endometrial cells is correlated with distinct cell phenotype, gene expression patterns, and proliferative responsiveness to serum and TGF-beta1 [9].
• These results suggest that BTEB, like Sp1, is involved in transcriptional activation of the HIV-1 LTR [3].

Anatomical context of KLF9

• Our findings define a novel pathway for BTEB1/PR cross-talk to facilitate P-dependent gene transcription in endometrial epithelial cells [1].
• This effect of BTEB was not observed in transfected endometrial stromal fibroblastic cells, but was apparent in the human endometrial epithelial carcinoma cell lines ECC-1 and Hec-1-A, which exhibit low levels of BTEB protein and low or undetectable PR mRNA levels, respectively [8].
• Northern blot analysis showed that various T cell and macrophage/monocyte cell lines expressed the BTEB mRNA to a level comparable with that of Sp1, another GC box-binding transcription factor [3].
• Human BTEB cDNA clones have been isolated, sequenced, and the corresponding gene has been assigned to human chromosome 9, region q13, by fluorescent in situ hybridization and DNA blot analysis using DNAs from hybrid cell clones containing a single human chromosome [10].
• In HeLa cells co-transfection with the GC-box-binding protein BTEB resulted in a 4-10-fold increase in hEF1A-1 promoter activity [11].

Associations of KLF9 with chemical compounds

• Unliganded PR inhibited luciferase activity in low and high BTEB backgrounds, and this effect was reversed by the synthetic progestin R5020 in both lines [12].
• These genes as well as three known to be TH regulated in other species and found in this study also in human cells (glucose transporter 1, solute carrier family 16 member 3, and basic transcription element-binding protein 1) have a variety of regulatory functions in development and metabolism [13].
• The transcription factor basic transcription element-binding protein 1 is a direct thyroid hormone response gene in the frog Xenopus laevis [14].
• Positivity for NKI/C3 was seen in 12 of 12 cases studied, and for NKI/Bteb in 12 of 13 cases [7].
• Triclosan exposure also resulted in decreased T(3)-mediated TRbeta mRNA expression in the tadpole tail fin and increased levels of PCNA transcript in the brain within 48h of T(3) treatment whereas TRalpha and BTEB were unaffected [15].

Other interactions of KLF9

• Under our conditions, the transcripts encoding KLF1 and KLF9 were never detected [16].
• cDNA cloning and transcriptional properties of a novel GC box-binding protein, BTEB2 [17].
• This protein represents a new homologue of BTEB1, originally described as a regulator of the BTE site in the CYP1A1 gene promoter [18].
• Taken together, the results suggest that BTEB1 mediates the expression of growth-associated genes through direct and indirect transactivation mechanisms, one of which may involve the participation of a JNK family member [19].
• 7,12-Dimethylbenzanthracene-dependent transcriptional regulation of adenomatous polyposis coli (APC) gene expression in normal breast epithelial cells is mediated by GC-box binding protein Sp3 [20].

Analytical, diagnostic and therapeutic context of KLF9

• Using mRNA differential display in the analysis of RNA populations from Hec-1-A sublines with high (4S, 9S) and low (2As, 3As) BTEB1 cellular content, we identified 10 distinct differentially expressed transcripts, nine of which had higher levels in S than in As sublines [19].
• To elucidate intracellular signaling pathways that might involve BTEB1, inhibitors of specific kinase-dependent transducers were used in transient transfection assays involving the IGFBP-2 gene promoter in 4S and 2As sublines [19].

References