* 300286

KRUPPEL-LIKE FACTOR 8; KLF8


Alternative titles; symbols

ZINC FINGER PROTEIN 741; ZNF741
BASIC KRUPPEL-LIKE FACTOR 3; BKLF3


HGNC Approved Gene Symbol: KLF8

Cytogenetic location: Xp11.21     Genomic coordinates (GRCh38): X:55,908,123-56,291,531 (from NCBI)


TEXT

Description

Kruppel-like factors (KLFs), such as KLF8, contain a characteristic C-terminal DNA-binding domain containing 3 Kruppel-like zinc fingers. KLFs recognize CACCC and GC boxes present in promoters and enhancers (summary by van Vliet et al., 2000).


Cloning and Expression

By searching an EST database for sequences related to BKLF (KLF3; 609392), followed by PCR, van Vliet et al. (2000) identified a cDNA encoding KLF8, also called ZNF741. Expression of KLF8 or only its zinc fingers showed that the fingers could bind to a CACCC box. Sequence analysis predicted that the 359-amino acid protein contains a nuclear localization signal upstream of the zinc fingers, a valine-rich hydrophobic stretch, and a pro-val-asp-leu-ser (PVDLS) motif. Yeast 2-hybrid and GST pull-down analysis demonstrated that CTBP2 (602619) interacts with KLF8 through the PVDLS motif. Reporter assays indicated that the N terminus of KLF8 can repress transcription mediated by a CACCC box-dependent promoter without using the CTBP2 contact motif. Northern blot analysis detected 3-, 6-, 7-, and 11-kb transcripts in most tissues tested, with most abundant expression in kidney, heart, and placenta.


Gene Structure

Lossi et al. (2002) determined that the KLF8 gene contains 6 exons and that exon 2 is alternatively spliced.


Mapping

Suske et al. (2005) stated that the human KLF8 gene maps to chromosome Xp11.21, and the mouse Klf8 gene to chromosome XF3.


Cytogenetics

Lossi et al. (2002) reported a girl with nonsyndromic mental retardation associated with a de novo balanced translocation t(X;21)(p11.2;q22.3) that interrupted the KLF8 gene. Analysis of her lymphoblasts showed absence of the KLF8 transcript, and all her normal X chromosomes were inactivated. However, the authors could not exclude a role for potential genes on chromosome 21q22. Direct sequencing of the KLF8 gene in 20 unrelated X-linked mental retardation (XLMR) families showing linkage to Xp11 did not identify pathogenic mutations, suggesting that disruption of the KLF8 gene is not a common cause of XLMR.


Animal Model

Funnell et al. (2013) found that Klf8 -/- males and females were viable and fertile, but that they had a significantly shortened lifespan compared with wildtype. Klf3 (609392) -/- mice were viable, but they were essentially infertile. Knockout of both Klf3 and Klf8 resulted in embryonic lethality, suggesting genetic interaction between the 2 genes. RT-PCR analysis showed that Klf8 expression was upregulated in Klf3 -/- erythroid tissues. Microarray assays revealed that fetal liver of Klf3 -/- Klf8 -/- embryos exhibited greater dysregulation of gene expression than either single mutant, particularly derepression of embryonic, but not adult, globin expression. Klf3 repressed expression of embryonic globin genes in erythroid cells, and Klf8 partially compensated in its absence.


REFERENCES

  1. Funnell, A. P. W., Mak, K. S., Twine, N. A., Pelka, G. J., Norton, L. J., Radziewic, T., Power, M., Wilkins, M. R., Bell-Anderson, K. S., Fraser, S. T., Perkins, A. C., Tam, P. P., Pearson, R. C. M., Crossley, M. Generation of mice deficient in both KLF3/BKLF and KLF8 reveals a genetic interaction and a role for these factors in embryonic globin gene silencing. Molec. Cell. Biol. 33: 2976-2987, 2013. [PubMed: 23716600, related citations] [Full Text]

  2. Lossi, A.-M., Laugier-Anfossi, F., Depetris, D., Gecz, J., Gedeon, A., Kooy, F., Schwartz, C., Mattei, M.-G., Croquette, M.-F., Villard, L. Abnormal expression of the KLF8 (ZNF741) gene in a female patient with an X;autosome translocation t(X;21)(p11.2;q22.3) and non-syndromic mental retardation. J. Med. Genet. 39: 113-117, 2002. [PubMed: 11836360, related citations] [Full Text]

  3. 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]

  4. van Vliet, J., Turner, J., Crossley, M. Human Kruppel-like factor 8: a CACCC-box binding protein that associates with CtBP and represses transcription. Nucleic Acids Res. 28: 1955-1962, 2000. [PubMed: 10756197, images, related citations] [Full Text]


Bao Lige - updated : 05/20/2020
Cassandra L. Kniffin - updated : 8/9/2011
Patricia A. Hartz - updated : 5/31/2005
Creation Date:
Paul J. Converse : 12/13/2000
carol : 05/21/2020
mgross : 05/20/2020
wwang : 08/10/2011
ckniffin : 8/9/2011
alopez : 7/7/2010
terry : 2/3/2006
wwang : 5/31/2005
mgross : 12/13/2000

* 300286

KRUPPEL-LIKE FACTOR 8; KLF8


Alternative titles; symbols

ZINC FINGER PROTEIN 741; ZNF741
BASIC KRUPPEL-LIKE FACTOR 3; BKLF3


HGNC Approved Gene Symbol: KLF8

Cytogenetic location: Xp11.21     Genomic coordinates (GRCh38): X:55,908,123-56,291,531 (from NCBI)


TEXT

Description

Kruppel-like factors (KLFs), such as KLF8, contain a characteristic C-terminal DNA-binding domain containing 3 Kruppel-like zinc fingers. KLFs recognize CACCC and GC boxes present in promoters and enhancers (summary by van Vliet et al., 2000).


Cloning and Expression

By searching an EST database for sequences related to BKLF (KLF3; 609392), followed by PCR, van Vliet et al. (2000) identified a cDNA encoding KLF8, also called ZNF741. Expression of KLF8 or only its zinc fingers showed that the fingers could bind to a CACCC box. Sequence analysis predicted that the 359-amino acid protein contains a nuclear localization signal upstream of the zinc fingers, a valine-rich hydrophobic stretch, and a pro-val-asp-leu-ser (PVDLS) motif. Yeast 2-hybrid and GST pull-down analysis demonstrated that CTBP2 (602619) interacts with KLF8 through the PVDLS motif. Reporter assays indicated that the N terminus of KLF8 can repress transcription mediated by a CACCC box-dependent promoter without using the CTBP2 contact motif. Northern blot analysis detected 3-, 6-, 7-, and 11-kb transcripts in most tissues tested, with most abundant expression in kidney, heart, and placenta.


Gene Structure

Lossi et al. (2002) determined that the KLF8 gene contains 6 exons and that exon 2 is alternatively spliced.


Mapping

Suske et al. (2005) stated that the human KLF8 gene maps to chromosome Xp11.21, and the mouse Klf8 gene to chromosome XF3.


Cytogenetics

Lossi et al. (2002) reported a girl with nonsyndromic mental retardation associated with a de novo balanced translocation t(X;21)(p11.2;q22.3) that interrupted the KLF8 gene. Analysis of her lymphoblasts showed absence of the KLF8 transcript, and all her normal X chromosomes were inactivated. However, the authors could not exclude a role for potential genes on chromosome 21q22. Direct sequencing of the KLF8 gene in 20 unrelated X-linked mental retardation (XLMR) families showing linkage to Xp11 did not identify pathogenic mutations, suggesting that disruption of the KLF8 gene is not a common cause of XLMR.


Animal Model

Funnell et al. (2013) found that Klf8 -/- males and females were viable and fertile, but that they had a significantly shortened lifespan compared with wildtype. Klf3 (609392) -/- mice were viable, but they were essentially infertile. Knockout of both Klf3 and Klf8 resulted in embryonic lethality, suggesting genetic interaction between the 2 genes. RT-PCR analysis showed that Klf8 expression was upregulated in Klf3 -/- erythroid tissues. Microarray assays revealed that fetal liver of Klf3 -/- Klf8 -/- embryos exhibited greater dysregulation of gene expression than either single mutant, particularly derepression of embryonic, but not adult, globin expression. Klf3 repressed expression of embryonic globin genes in erythroid cells, and Klf8 partially compensated in its absence.


REFERENCES

  1. Funnell, A. P. W., Mak, K. S., Twine, N. A., Pelka, G. J., Norton, L. J., Radziewic, T., Power, M., Wilkins, M. R., Bell-Anderson, K. S., Fraser, S. T., Perkins, A. C., Tam, P. P., Pearson, R. C. M., Crossley, M. Generation of mice deficient in both KLF3/BKLF and KLF8 reveals a genetic interaction and a role for these factors in embryonic globin gene silencing. Molec. Cell. Biol. 33: 2976-2987, 2013. [PubMed: 23716600] [Full Text: https://doi.org/10.1128/MCB.00074-13]

  2. Lossi, A.-M., Laugier-Anfossi, F., Depetris, D., Gecz, J., Gedeon, A., Kooy, F., Schwartz, C., Mattei, M.-G., Croquette, M.-F., Villard, L. Abnormal expression of the KLF8 (ZNF741) gene in a female patient with an X;autosome translocation t(X;21)(p11.2;q22.3) and non-syndromic mental retardation. J. Med. Genet. 39: 113-117, 2002. [PubMed: 11836360] [Full Text: https://doi.org/10.1136/jmg.39.2.113]

  3. 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]

  4. van Vliet, J., Turner, J., Crossley, M. Human Kruppel-like factor 8: a CACCC-box binding protein that associates with CtBP and represses transcription. Nucleic Acids Res. 28: 1955-1962, 2000. [PubMed: 10756197] [Full Text: https://doi.org/10.1093/nar/28.9.1955]


Contributors:
Bao Lige - updated : 05/20/2020
Cassandra L. Kniffin - updated : 8/9/2011
Patricia A. Hartz - updated : 5/31/2005

Creation Date:
Paul J. Converse : 12/13/2000

Edit History:
carol : 05/21/2020
mgross : 05/20/2020
wwang : 08/10/2011
ckniffin : 8/9/2011
alopez : 7/7/2010
terry : 2/3/2006
wwang : 5/31/2005
mgross : 12/13/2000