Alternative titles; symbols
HGNC Approved Gene Symbol: ZNF146
Cytogenetic location: 19q13.12 Genomic coordinates (GRCh38): 19:36,214,723-36,238,768 (from NCBI)
ZNF146 is a DNA-binding zinc finger protein that targets LINE-1 transposable elements (TEs) (Creamer et al., 2022).
Le Chalony et al. (1994) identified a cDNA, designated OZF by them (for 'only zinc fingers'), that codes for a member of the Kruppel subfamily of zinc finger proteins (see 194631). In contrast to most of the Kruppel zinc finger proteins, the putative product of the OZF gene encodes a polypeptide solely composed of 10 zinc finger motifs and appears to be devoid of a non-zinc finger regulatory domain for interactions with other proteins.
Ferbus et al. (1996) reported the characterization of the human OZF protein. Immunochemical analysis using antibodies produced against the recombinant protein detected its expression in human mammary epithelial cells but not in stroma cells, which is consistent with the pattern of expression observed at the RNA level within cell cultures. Western blot analysis demonstrated the expression of a 33-kD nuclear protein similar in size to the predicted protein and, therefore, excluded the presence of an additional transfer-activating domain. The data established the unique structure of the OZF protein which is distinct from previously identified zinc finger proteins. In addition, OZF protein overexpression was found in a tumor cell line, which suggests a possible involvement in carcinogenesis.
Blottiere et al. (1999) cloned mouse Znf146, which they called Zpf146, from a liver cDNA library. The deduced protein contains 10 Kruppel-type zinc fingers. It shares 95% amino acid identity with bovine and human ZNF146, and the last 4 zinc fingers are identical between the 3 species. Northern blot analysis detected Zfp146 expression in all mouse tissues examined, with highest levels in heart, brain, lung, liver, skeletal muscle, and kidney. A similar expression profile was found for Zfp260 (ZNF260; 613749), which is closely related to Zfp146.
Pibouin et al. (2001) cloned human ZNF146 cDNA from a genomic library specific for human chromosome 19 and identified and characterized its regulatory region. The ZNF146 gene is transcribed in at least 2 splice variants coexisting in the same cell type, and encodes a protein consisting solely of 10 zinc finger motifs.
Ferbus et al. (1996) found that the human OZF protein produced in E. coli bound zinc ions, DNA, and heparin. These binding activities are characteristic of zinc finger proteins.
By chromatin immunoprecipitation-sequencing analysis, Creamer et al. (2022) identified ZNF146 and ZNF507 (620567) as DNA-binding proteins that targeted TEs. Both ZNF146 and ZNF507 preferentially bound to LINE-1 transposons. LINE-1 transposons code for 2 proteins by ORF1 and ORF2. ZNF146 and ZNF507 targeted sequences within ORF2, but not within ORF1, and ZNF146 and ZNF507 binding occurred at opposite ends of ORF2. Moreover, ZNF146 binding sites were found at both old and young LINE-1 elements, whereas ZNF507 preferentially bound young LINE-1 sequences, likely due to amino acid substitutions in its zinc fingers during evolution. ZNF146 depletion did not result in differential expression of genes in HEK293 cells, whereas ZNF507 depletion resulted in differential expression of 32 genes in HEK293 cells.
Pibouin et al. (2001) determined that the human ZNF146 gene consists of 5 exons spanning a 25-kb genomic region. Exon 5 is the largest and only coding exon.
Le Chalony et al. (1994) reported that the OZF gene maps to chromosome 19q31.1. Le Chalony et al. (1996) found additional OZF sequences in cow and zebu that were amplified on the X chromosome.
Using FISH, Blottiere et al. (1999) mapped the mouse Zfp146 and Zfp260 genes to chromosome 7B1-B3, which shares homology of synteny with human chromosome 19q13.1.
Blottiere, L., Apiou, F., Ferbus, D., Guenzi, C., Dutrillaux, B., Prosperi, M.-T., Goubin, G. Cloning, characterization, and chromosome assignment of Zfp146 the mouse ortholog of human ZNF146, a gene amplified and overexpressed in pancreatic cancer, and Zfp260 a closely related gene. Cytogenet. Cell Genet. 85: 297-300, 1999. [PubMed: 10449921] [Full Text: https://doi.org/10.1159/000015316]
Creamer, K. M., Larsen, E. C., Lawrence, J. B. ZNF146/OZF and ZNF507 target LINE-1 sequences. G3 12: jkac002, 2022. [PubMed: 35100360] [Full Text: https://doi.org/10.1093/g3journal/jkac002]
Ferbus, D., Le Chalony, C., Prosperi, M.-T., Muleris, M., Vincent-Salomon, A., Goubin, G. Identification, nuclear localization, and binding activities of OZF, a human protein solely composed of zinc finger motifs. Europ. J. Biochem. 236: 991-995, 1996. [PubMed: 8665923] [Full Text: https://doi.org/10.1111/j.1432-1033.1996.00991.x]
Le Chalony, C., Apiou, F., Pibouin, L., Dutrillaux, B., Goubin, G. Constitutive amplification of a zinc finger protein gene in cattle. DNA Cell Biol. 15: 83-88, 1996. [PubMed: 8561900] [Full Text: https://doi.org/10.1089/dna.1996.15.83]
Le Chalony, C., Prosperi, M.-T., Haluza, R., Apiou, F., Dutrillaux, B., Goubin, G. The OZF gene encodes a protein consisting essentially of zinc-finger motifs. J. Molec. Biol. 236: 399-404, 1994. [PubMed: 8107129] [Full Text: https://doi.org/10.1006/jmbi.1994.1151]
Pibouin, L., Villaudy, J., Prosperi, M.-T., Goubin, G. Genomic organization and promoter identification of ZNF146, a gene encoding a protein consisting solely of zinc finger domains. Cytogenet. Cell Genet. 92: 80-84, 2001. [PubMed: 11306801] [Full Text: https://doi.org/10.1159/000056873]