Alternative titles; symbols
Other entities represented in this entry:
HGNC Approved Gene Symbol: PATZ1
Cytogenetic location: 22q12.2 Genomic coordinates (GRCh38) : 22:31,325,804-31,346,346 (from NCBI)
BTB/POZ (broad complex, tramtrack, and bric-a-brac/poxvirus and zinc finger) domains direct specific protein-protein interactions and are frequently present in transcription factors. Using a yeast 2-hybrid screen with RING finger protein-4 (RNF4; 602850) as bait, followed by screening a breast carcinoma cDNA library, Fedele et al. (2000) isolated a cDNA encoding ZNF278, which they called PATZ (POZ-AT hook-zinc finger protein). The predicted 537-amino acid ZNF278 protein contains an N-terminal BTB/POZ domain, an AT-hook DNA-binding domain typical of HMG1 proteins (see 163905), and a 7-zinc finger domain. The first 4 zinc fingers are of the C2H2 type, while the last 3 fingers have a substitution in a hydrophobic residue that may stabilize the formation of the zinc finger. Fedele et al. (2000) also identified nuclear localization signals within the AT-hook domain and between zinc fingers 1 and 2.
Using a yeast 2-hybrid screen with the BTB/POZ domain of Bach2 (see BACH1; 602751) as bait, Kobayashi et al. (2000) isolated a mouse cDNA encoding Znf278, which they called Mazr (MAZ (600999)-related factor). By searching sequence databases, Kobayashi et al. (2000) identified a human genomic sequence encoding ZNF278, which shares 99% amino acid identity with mouse Znf278. Northern blot analysis detected mouse Znf278 transcripts in thymus, fetal liver, and bone marrow, as well as in other tissues at lower levels.
Mastrangelo et al. (2000) cloned ZNF278, which they called ZSG, by 5-prime RACE, cDNA library and database screening, and sequence analysis of a PAC clone. RT-PCR analysis showed that exon 5 is subject to alternative splicing, resulting in proteins with either 4 or 6 C2H2 zinc fingers at the C terminus. Northern blot analysis revealed ubiquitous expression of 3- and 4-kb transcripts.
By chromatographic and coimmunoprecipitation analyses, Fedele et al. (2000) showed that ZNF278 interacts with RNF4 both in vitro and in vivo. The authors found that the POZ domain is responsible for repression of basal transcription as well as repression of RNF4-mediated activation. Immunofluorescence analysis demonstrated that ZNF278 colocalizes with RNF4 in the nuclear matrix.
Kobayashi et al. (2000) found that mouse Znf278 is a transcriptional activator of the c-myc (190080) promoter and that transcriptional activation is enhanced in the presence of Bach2; the interaction of Znf278 and Bach2 occurs through the BTB/POZ domain.
In mice, at least 5 Cd8 cis-acting enhancers, individually or in combination, direct expression in the T-cell lineage, and deletion of specific enhancers leads to variegated expression of Cd8a (186910)/Cd8b (186730) heterodimers in double-positive thymocytes. Bilic et al. (2006) showed that Cd8 variegation due to enhancer deletion correlated with an epigenetic 'off' state, linking Cd8 enhancer function with chromatin remodeling of Cd8a and Cd8b. The zinc finger protein Mazr bound the Cd8 enhancer and, via its N-terminal domain, interacted with the Ncor1 (600849) complex in double-negative thymocytes. Mazr was downregulated in double-positive and Cd8 single-positive thymocytes. Constitutive expression of Mazr during T-cell development resulted in variegated expression of Cd8 in double-positive thymocytes. Bilic et al. (2006) concluded that MAZR is a negative regulator of CD8 expression in double-negative thymocytes.
Mastrangelo et al. (2000) determined that the ZNF278 gene contains 6 exons and spans 20 kb.
Kobayashi et al. (2000) identified a human sequence encoding ZNF278 in 22q12; they confirmed this localization using a radiation hybrid panel.
Mastrangelo et al. (2000) describe a submicroscopic inversion of chromosome 22q in a small round cell sarcoma with a t(1;22)(p36.1;q12) translocation. The resultant chimeric transcript contained exon 8 of the Ewing sarcoma gene (EWS; 133450) fused in-frame to exon 1 of the ZNF278 gene, creating a protein with the transactivation domain of EWS fused to the zinc finger domain of ZNF278. Mastrangelo et al. (2000) found that the ZNF278 gene is located 2 Mb distal to EWS and is transcribed in the opposite orientation. Thus, they concluded that a paracentric inversion of 22q12 should have occurred in order to create the active EWS-ZNF278 fusion gene.
Modena et al. (2003) characterized a translocation t(1;22)(p34;q12) that was associated with a paracentric inversion of chromosome 22q12 in a small round cell sarcoma. They had previously shown (Mastrangelo et al., 2000) that the inversion of chromosome 22q12 generated an EWS/ZSG fusion gene. Modena et al. (2003) found that the t(1;22)(p34;q12) interrupted the UQCRH gene (613844), with the breakpoint in intron 3, and created fusion genes with both EWS on der(22) and ZSG on der(1). PCR analysis of tumor cDNA and genomic DNA detected 5-prime-UQCRH/EWS-3-prime, 5-prime-ZSG/UQCRH-3-prime, and 5-prime-EWS/ZSG-3-prime. Only 5-prime-EWS/ZSG-3-prime produced in-frame transcripts. In contrast, 5-prime-UQCRH/EWS-3-prime and 5-prime-ZSG/UQCRH-3-prime produced out-of-frame transcripts containing premature stop codons.
Bilic, I., Koesters, C., Unger, B., Sekimata, M., Hertweck, A., Maschek, R., Wilson, C. B., Ellmeier, W. Negative regulation of CD8 expression via Cd8 enhancer-mediated recruitment of the zinc finger protein MAZR. Nature Immun. 7: 392-400, 2006. [PubMed: 16491076] [Full Text: https://doi.org/10.1038/ni1311]
Fedele, M., Benvenuto, G., Pero, R., Majello, B., Battista, S., Lembo, F., Vollono, E., Day, P. M., Santoro, M., Lania, L., Bruni, C. B., Fusco, A., Chiariotti, L. A novel member of the BTB/POZ family, PATZ, associates with the RNF4 RING finger protein and acts as a transcriptional repressor. J. Biol. Chem. 275: 7894-7901, 2000. [PubMed: 10713105] [Full Text: https://doi.org/10.1074/jbc.275.11.7894]
Kobayashi, A., Yamagiwa, H., Hoshino, H., Muto, A., Sato, K., Morita, M., Hayashi, N., Yamamoto, M., Igarashi, K. A combinatorial code for gene expression generated by transcription factor Bach2 and MAZR (MAZ-related factor) through the BTB/POZ domain. Molec. Cell. Biol. 20: 1733-1746, 2000. [PubMed: 10669750] [Full Text: https://doi.org/10.1128/MCB.20.5.1733-1746.2000]
Mastrangelo, T., Modena, P., Tornielli, S., Bullrich, F., Testi, M. A., Mezzelani, A., Radice, P., Azzarelli, A., Pilotti, S., Croce, C. M., Pierotti, M. A., Sozzi, G. A novel zinc finger gene is fused to EWS in small round cell tumor. Oncogene 19: 3799-3804, 2000. [PubMed: 10949935] [Full Text: https://doi.org/10.1038/sj.onc.1203762]
Modena, P., Testi, M. A., Facchinetti, F., Mezzanzanica, D., Radice, M. T., Pilotti, S., Sozzi, G. UQCRH gene encoding mitochondrial hinge protein is interrupted by a translocation in a soft-tissue sarcoma and epigenetically inactivated in some cancer cell lines. Oncogene 22: 4586-4593, 2003. [PubMed: 12881716] [Full Text: https://doi.org/10.1038/sj.onc.1206472]