* 601878

KRUPPEL-LIKE FACTOR 10; KLF10


Alternative titles; symbols

TRANSFORMING GROWTH FACTOR-BETA-INDUCIBLE EARLY GROWTH RESPONSE; TIEG
TGFB-INDUCIBLE EARLY GROWTH RESPONSE
TGF-BETA-INDUCIBLE EARLY GENE
ZINC FINGER TRANSCRIPTION FACTOR TIEG
TRANSFORMING GROWTH FACTOR-BETA-INDUCIBLE EARLY GROWTH RESPONSE 1; TIEG1
EARLY GROWTH RESPONSE-ALPHA


HGNC Approved Gene Symbol: KLF10

Cytogenetic location: 8q22.3     Genomic coordinates (GRCh38): 8:102,648,784-102,655,725 (from NCBI)


TEXT

Cloning and Expression

Tachibana et al. (1997) characterized the expression in exocrine pancreatic epithelial cells of KLF10, which they called TIEG, a Kruppel-like zinc finger transcription factor-encoding gene previously isolated from mesodermally derived osteoblastic cells by Subramaniam et al. (1995). Tachibana et al. (1997) demonstrated that the gene was expressed in both acinar and ductular epithelial cell populations from the exocrine pancreas.

By comparative sequencing, Fautsch et al. (1998) determined that TIEG and EGR-alpha (Blok et al., 1995) are expressed from alternative promoters of the same gene. Use of alternative first exons results in TIEG having 12 unique amino acids on its N terminus. Northern blot analysis with a TIEG-specific probe detected expression in all tissues tested, with highest levels in peripheral blood leukocytes, spleen, and colon, and lower levels in thymus, small intestine, ovary, and prostate. Expression was also found in all muscle types, with highest expression in skeletal muscle. In contrast, Northern blot analysis with an EGR-alpha-specific probe detected no expression in any tissues tested.


Gene Function

Members of the TGF-beta (TGFB1; 190180) family of peptides exert antiproliferative effects and induce apoptosis in epithelial cell populations. In the exocrine pancreas these peptides not only regulate normal cell growth, but alterations in these pathways have been associated with neoplastic transformation. Tachibana et al. (1997) showed that expression of TIEG was regulated by TGF-beta as an early-response gene in pancreatic epithelial cell lines. Overexpression of TIEG in a TGF-beta-sensitive epithelial cell line was sufficient to induce apoptosis. Tachibana et al. (1997) concluded that TIEG plays a role in linking TGF-beta-mediated signaling cascades to the regulation of pancreatic epithelial cell growth.

Ivanov et al. (2008) found that VHL (608537) upregulated expression of TGFBI (601692) in 786-0 renal clear-cell carcinoma cells. The effect was mediated by VHL-dependent downregulation of KLF10, which recognized SP1 (189906)-binding sites in the TGFBI promoter and activated expression of a TGFBI reporter gene.

Using cultured embryonic chicken myoblasts and differentiated myotubes, Parakati and DiMario (2013) found that expression of human KLF10 downregulated Fgfr1 (136350) and cell proliferation by binding a specific Sp1 site in the Fgfr1 proximal promoter. Binding of KLF10 to this site inhibited formation of transactivating Sp1 complexes. Parakati and DiMario (2013) concluded that KLF10 is a repressor of myoblast proliferation.


Gene Structure

Fautsch et al. (1998) determined that the TIEG gene contains 5 exons and spans 8 kb of genomic DNA. Alternative promoters produce the TIEG and EGR-alpha variants. Analysis of constructs containing 5-prime-flanking regions showed that both the TIEG and the EGR-alpha promoters have significant activity in human fetal osteoblast cells.

Fautsch et al. (1998) compared the genomic structures of the human and mouse TIEG genes.


Mapping

Suske et al. (2005) stated that the human KLF10 gene maps to chromosome 8q22.2 and that the mouse Klf10 gene maps to chromosome 1C5.


REFERENCES

  1. Blok, L. J., Grossmann, M. E., Perry, J. E., Tindall, D. J. Characterization of an early growth response gene which encodes a zinc finger transcription factor potentially involved in cell cycle regulation. Molec. Endocr. 9: 1610-1620, 1995. [PubMed: 8584037, related citations] [Full Text]

  2. Fautsch, M. P., Vrabel, A., Rickard, D., Subramaniam, M., Spelsberg, T. C., Wieben, E. D. Characterization of the mouse TGF-beta-inducible early gene (TIEG): conservation of exon and transcriptional regulatory sequences with evidence of additional transcripts. Mammalian Genome 9: 838-842, 1998. [PubMed: 9745041, related citations] [Full Text]

  3. Fautsch, M. P., Vrabel, A., Subramaniam, M., Hefferen, T. E., Spelsberg, T. C., Wieben, E. D. TGF-beta-inducible early gene (TIEG) also codes for early growth response alpha (EGR-alpha): evidence of multiple transcripts from alternate promoters. Genomics 51: 408-416, 1998. [PubMed: 9721211, related citations] [Full Text]

  4. Ivanov, S. V., Ivanova, A. V., Salnikow, K., Timofeeva, O., Subramaniam, M., Lerman, M. I. Two novel VHL targets, TGFBI (BIGH3) and its transactivator KLF10, are up-regulated in renal clear cell carcinoma and other tumors. Biochem . Biophys. Res. Commun. 370: 536-540, 2008. [PubMed: 18359287, images, related citations] [Full Text]

  5. Parakati, R., DiMario, J. X. Repression of myoblast proliferation and fibroblast growth factor receptor 1 promoter activity by KLF10 protein. J. Biol. Chem. 288: 13876-13884, 2013. [PubMed: 23569208, images, related citations] [Full Text]

  6. Subramaniam, M., Harris, S. A., Oursler, M. J., Rasmussen, K., Riggs, B. L., Spelsberg, T. C. Identification of a novel TGF-beta-regulated gene encoding a putative zinc finger protein in human osteoblasts. Nucleic Acids Res. 23: 4907-4912, 1995. [PubMed: 8532536, related citations] [Full Text]

  7. Suske, G., Bruford, E., Philipsen, S. Mammalian SP/KLF transcription factors: bring in the family. Genomics 85: 551-556, 2005. [PubMed: 15820306, related citations] [Full Text]

  8. Tachibana, I., Imoto, M., Adjei, P. N., Gores, G. J., Subramaniam, M., Spelsberg, T. C., Urrutia, R. Overexpression of the TGF-beta-regulated zinc finger encoding gene, TIEG, induces apoptosis in pancreatic epithelial cells. J. Clin. Invest. 99: 2365-2374, 1997. [PubMed: 9153278, related citations] [Full Text]


Patricia A. Hartz - updated : 2/7/2014
Patricia A. Hartz - updated : 5/31/2005
Carol A. Bocchini - updated : 5/21/2001
Victor A. McKusick - updated : 10/5/1998
Creation Date:
Victor A. McKusick : 6/19/1997
carol : 05/04/2022
carol : 04/07/2022
carol : 09/20/2016
mgross : 02/12/2014
mcolton : 2/7/2014
wwang : 5/31/2005
mcapotos : 5/23/2001
carol : 5/21/2001
psherman : 11/19/1998
psherman : 11/19/1998
carol : 10/7/1998
terry : 10/5/1998
mark : 8/26/1997
alopez : 6/23/1997
jenny : 6/23/1997
alopez : 6/19/1997

* 601878

KRUPPEL-LIKE FACTOR 10; KLF10


Alternative titles; symbols

TRANSFORMING GROWTH FACTOR-BETA-INDUCIBLE EARLY GROWTH RESPONSE; TIEG
TGFB-INDUCIBLE EARLY GROWTH RESPONSE
TGF-BETA-INDUCIBLE EARLY GENE
ZINC FINGER TRANSCRIPTION FACTOR TIEG
TRANSFORMING GROWTH FACTOR-BETA-INDUCIBLE EARLY GROWTH RESPONSE 1; TIEG1
EARLY GROWTH RESPONSE-ALPHA


HGNC Approved Gene Symbol: KLF10

Cytogenetic location: 8q22.3     Genomic coordinates (GRCh38): 8:102,648,784-102,655,725 (from NCBI)


TEXT

Cloning and Expression

Tachibana et al. (1997) characterized the expression in exocrine pancreatic epithelial cells of KLF10, which they called TIEG, a Kruppel-like zinc finger transcription factor-encoding gene previously isolated from mesodermally derived osteoblastic cells by Subramaniam et al. (1995). Tachibana et al. (1997) demonstrated that the gene was expressed in both acinar and ductular epithelial cell populations from the exocrine pancreas.

By comparative sequencing, Fautsch et al. (1998) determined that TIEG and EGR-alpha (Blok et al., 1995) are expressed from alternative promoters of the same gene. Use of alternative first exons results in TIEG having 12 unique amino acids on its N terminus. Northern blot analysis with a TIEG-specific probe detected expression in all tissues tested, with highest levels in peripheral blood leukocytes, spleen, and colon, and lower levels in thymus, small intestine, ovary, and prostate. Expression was also found in all muscle types, with highest expression in skeletal muscle. In contrast, Northern blot analysis with an EGR-alpha-specific probe detected no expression in any tissues tested.


Gene Function

Members of the TGF-beta (TGFB1; 190180) family of peptides exert antiproliferative effects and induce apoptosis in epithelial cell populations. In the exocrine pancreas these peptides not only regulate normal cell growth, but alterations in these pathways have been associated with neoplastic transformation. Tachibana et al. (1997) showed that expression of TIEG was regulated by TGF-beta as an early-response gene in pancreatic epithelial cell lines. Overexpression of TIEG in a TGF-beta-sensitive epithelial cell line was sufficient to induce apoptosis. Tachibana et al. (1997) concluded that TIEG plays a role in linking TGF-beta-mediated signaling cascades to the regulation of pancreatic epithelial cell growth.

Ivanov et al. (2008) found that VHL (608537) upregulated expression of TGFBI (601692) in 786-0 renal clear-cell carcinoma cells. The effect was mediated by VHL-dependent downregulation of KLF10, which recognized SP1 (189906)-binding sites in the TGFBI promoter and activated expression of a TGFBI reporter gene.

Using cultured embryonic chicken myoblasts and differentiated myotubes, Parakati and DiMario (2013) found that expression of human KLF10 downregulated Fgfr1 (136350) and cell proliferation by binding a specific Sp1 site in the Fgfr1 proximal promoter. Binding of KLF10 to this site inhibited formation of transactivating Sp1 complexes. Parakati and DiMario (2013) concluded that KLF10 is a repressor of myoblast proliferation.


Gene Structure

Fautsch et al. (1998) determined that the TIEG gene contains 5 exons and spans 8 kb of genomic DNA. Alternative promoters produce the TIEG and EGR-alpha variants. Analysis of constructs containing 5-prime-flanking regions showed that both the TIEG and the EGR-alpha promoters have significant activity in human fetal osteoblast cells.

Fautsch et al. (1998) compared the genomic structures of the human and mouse TIEG genes.


Mapping

Suske et al. (2005) stated that the human KLF10 gene maps to chromosome 8q22.2 and that the mouse Klf10 gene maps to chromosome 1C5.


REFERENCES

  1. Blok, L. J., Grossmann, M. E., Perry, J. E., Tindall, D. J. Characterization of an early growth response gene which encodes a zinc finger transcription factor potentially involved in cell cycle regulation. Molec. Endocr. 9: 1610-1620, 1995. [PubMed: 8584037] [Full Text: https://doi.org/10.1210/mend.9.11.8584037]

  2. Fautsch, M. P., Vrabel, A., Rickard, D., Subramaniam, M., Spelsberg, T. C., Wieben, E. D. Characterization of the mouse TGF-beta-inducible early gene (TIEG): conservation of exon and transcriptional regulatory sequences with evidence of additional transcripts. Mammalian Genome 9: 838-842, 1998. [PubMed: 9745041] [Full Text: https://doi.org/10.1007/s003359900878]

  3. Fautsch, M. P., Vrabel, A., Subramaniam, M., Hefferen, T. E., Spelsberg, T. C., Wieben, E. D. TGF-beta-inducible early gene (TIEG) also codes for early growth response alpha (EGR-alpha): evidence of multiple transcripts from alternate promoters. Genomics 51: 408-416, 1998. [PubMed: 9721211] [Full Text: https://doi.org/10.1006/geno.1998.5388]

  4. Ivanov, S. V., Ivanova, A. V., Salnikow, K., Timofeeva, O., Subramaniam, M., Lerman, M. I. Two novel VHL targets, TGFBI (BIGH3) and its transactivator KLF10, are up-regulated in renal clear cell carcinoma and other tumors. Biochem . Biophys. Res. Commun. 370: 536-540, 2008. [PubMed: 18359287] [Full Text: https://doi.org/10.1016/j.bbrc.2008.03.066]

  5. Parakati, R., DiMario, J. X. Repression of myoblast proliferation and fibroblast growth factor receptor 1 promoter activity by KLF10 protein. J. Biol. Chem. 288: 13876-13884, 2013. [PubMed: 23569208] [Full Text: https://doi.org/10.1074/jbc.M113.457648]

  6. Subramaniam, M., Harris, S. A., Oursler, M. J., Rasmussen, K., Riggs, B. L., Spelsberg, T. C. Identification of a novel TGF-beta-regulated gene encoding a putative zinc finger protein in human osteoblasts. Nucleic Acids Res. 23: 4907-4912, 1995. [PubMed: 8532536] [Full Text: https://doi.org/10.1093/nar/23.23.4907]

  7. Suske, G., Bruford, E., Philipsen, S. Mammalian SP/KLF transcription factors: bring in the family. Genomics 85: 551-556, 2005. [PubMed: 15820306] [Full Text: https://doi.org/10.1016/j.ygeno.2005.01.005]

  8. Tachibana, I., Imoto, M., Adjei, P. N., Gores, G. J., Subramaniam, M., Spelsberg, T. C., Urrutia, R. Overexpression of the TGF-beta-regulated zinc finger encoding gene, TIEG, induces apoptosis in pancreatic epithelial cells. J. Clin. Invest. 99: 2365-2374, 1997. [PubMed: 9153278] [Full Text: https://doi.org/10.1172/JCI119418]


Contributors:
Patricia A. Hartz - updated : 2/7/2014
Patricia A. Hartz - updated : 5/31/2005
Carol A. Bocchini - updated : 5/21/2001
Victor A. McKusick - updated : 10/5/1998

Creation Date:
Victor A. McKusick : 6/19/1997

Edit History:
carol : 05/04/2022
carol : 04/07/2022
carol : 09/20/2016
mgross : 02/12/2014
mcolton : 2/7/2014
wwang : 5/31/2005
mcapotos : 5/23/2001
carol : 5/21/2001
psherman : 11/19/1998
psherman : 11/19/1998
carol : 10/7/1998
terry : 10/5/1998
mark : 8/26/1997
alopez : 6/23/1997
jenny : 6/23/1997
alopez : 6/19/1997