Alternative titles; symbols
HGNC Approved Gene Symbol: MZF1
Cytogenetic location: 19q13.43 Genomic coordinates (GRCh38): 19:58,561,932-58,573,573 (from NCBI)
Zinc finger genes encode metal-binding proteins that can act as transcriptional regulators of other genes. In an effort to identify activators of the genetic cascade in hemopoietic differentiation, Hromas et al. (1991) used degenerate synthetic oligonucleotides to the conserved zinc finger histidine-cysteine link to probe a human myeloid lambda gt11 cDNA library. One of the cDNA clones obtained hybridized preferentially to mRNA from myeloid cells. Sequence analysis of the coding region for the gene demonstrated 13 zinc finger regions and a glycine-proline-rich region between the fourth and fifth zinc finger domains. This novel zinc finger gene, which they designated MZF1, was preferentially expressed in myeloid leukemia cell lines, with highest mRNA levels in cells induced to differentiate with retinoic acid.
By screening a human erythroleukemia K562 cell line cDNA library, followed by 5-prime and 3-prime RACE of normal human bone marrow mRNA, Peterson and Morris (2000) cloned 2 splice variants of MZF1, which they called MZF1B and MZF1C, that differed in their 5-prime ends. Both transcripts encode an identical 734-amino acid protein, MZF1B/C, that has an N-terminal extension compared with the 485-amino acid MZF1 protein. The N-terminal domain of MZF1B/C includes a SCAN domain, which is predicted to mediate protein-protein interactions, and this is followed by all but the first 8 amino acids of the MZF1 protein, including the acidic region and bipartite zinc finger domain. Northern blot analysis detected both MZF1 and MZF1B transcripts of about 3 kb in K562 cells. In vitro translation followed by SDS-PAGE showed that MZF1 and MZF1B had apparent molecular masses of 50 and 80 kD, respectively.
Gaboli et al. (2001) found that mouse Mzf1 was expressed in adult brain, testis, keratinocytes, thymus, and bone marrow.
The MZF1 gene is a putative transcription factor of the C2H2 zinc finger gene family. Morris et al. (1995) found that MZF1 regulated the CD34 (142230) promoter in a tissue-specific manner. They had previously demonstrated MZF1 binding sites in the promoters of several genes expressed during myeloid differentiation.
Using reporter gene assays, Liu et al. (2017) identified a core promoter and a separate functional MZF1-binding site within the PYROXD2 (617889) promoter region. Overexpression of MZF1 elevated endogenous PYROXD2 expression in human hepatic cells.
Shima et al. (2021) identified a conserved binding site for MZF1 in the promoter region of human CLDND1 (619677) and subsequently confirmed MZF1 binding experimentally. MZF1 bound the CLDND1 promoter and functioned as a transcription factor to regulate CLDND1 expression. Overexpression of MZF1 activated CLDND1 expression at both the mRNA and protein levels in HBECs. In contrast, knockdown of MZF1 reduced CLDND1 expression at both the mRNA and protein levels, resulting in increased vascular permeability of human brain endothelial cells.
Peterson and Morris (2000) determined that the MZF1 gene contains 6 exons and spans about 11.2 kb. Exon 1 is noncoding. The MZF1 transcript initiates within intron 5 and includes only exon 6 as a coding exon.
Hromas et al. (1991) mapped the MZF1 gene to chromosome 19q13.2-q13.4 by in situ hybridization and confirmed the localization by hybridization of a labeled probe to dot blots of flow-sorted chromosomes. Chromosome 19 contains other zinc finger genes, e.g., ZFP36 (190700), which is located at 19q13.1.
Gaboli et al. (2001) obtained Mzf1 -/- mice at the expected mendelian ratio and found that they developed normally. The ability of myeloid and lymphoid cells to differentiate was unimpaired in Mzf1 -/- mice, but they accumulated Mac1 (see ITGAM; 120980)-positive myeloid cells in bone marrow. By year 2, all Mzf1 -/- mice developed extramedullary hematopoiesis in liver or spleen, and about 30% developed a lethal neoplastic disease in which monomorphic blastic cells completely effaced the liver architecture. The morphologic features of these cells were characteristic of hematopoietic blasts with prominent nuclei. The bone marrow of Mzf1 -/- mice was almost invariably hypercellular, and 14% of Mzf1 -/- mice developed high-grade B-cell lymphoma. Mzf1 inactivation resulted in marked increases in both myeloid and erythroid colonies in culture, increased proliferation of hematopoietic progenitor cells, and increased long-term proliferative potential of hematopoietic progenitors. Gaboli et al. (2001) concluded that MZF1 functions as a tumor/growth suppressor in the hematopoietic compartment.
Gaboli, M., Kotsi, P. A., Gurrieri, C., Cattoretti, G., Ronchetti, S., Cordon-Cardo, C., Broxmeyer, H. E., Hromas, R., Pandolfi, P. P. Mzf1 controls cell proliferation and tumorigenesis. Genes Dev. 15: 1625-1630, 2001. [PubMed: 11445537] [Full Text: https://doi.org/10.1101/gad.902301]
Hromas, R., Collins, S. J., Hickstein, D., Raskind, W., Deaven, L. L., O'Hara, P., Hagen, F. S., Kaushansky, K. A retinoic acid-responsive human zinc finger gene, MZF-1, preferentially expressed in myeloid cells. J. Biol. Chem. 266: 14183-14187, 1991. [PubMed: 1860835]
Liu, H., Jiang, X., Wang, T., Yu, F., Wang, X., Chen, J., Xie, X., Fan, H. Myeloid zinc finger 1 protein is a key transcription stimulating factor of PYROXD2 promoter. Oncol. Rep. 38: 3245-3253, 2017. [PubMed: 29048625] [Full Text: https://doi.org/10.3892/or.2017.5990]
Morris, J. F., Rauscher, F. J., III, Davis, B., Klemsz, M., Xu, D., Tenen, D., Hromas, R. The myeloid zinc finger gene, MZF-1, regulates the CD34 promoter in vitro. Blood 86: 3640-3647, 1995. [PubMed: 7579328]
Peterson, M. J., Morris, J. F. Human myeloid zinc finger gene MZF produces multiple transcripts and encodes a SCAN box protein. Gene 254: 105-118, 2000. [PubMed: 10974541] [Full Text: https://doi.org/10.1016/s0378-1119(00)00281-x]
Shima, A., Matsuoka, H., Yamaoka, A., Michihara, A. Transcription of CLDN1 in human brain endothelial cells is regulated by the myeloid zinc finger 1. Clin. Exp. Pharmacol. Physiol. 48: 260-269, 2021. [PubMed: 33037622] [Full Text: https://doi.org/10.1111/1440-1681.13416]