HGNC Approved Gene Symbol: ZNF91
Cytogenetic location: 19p12 Genomic coordinates (GRCh38) : 19:23,305,004-23,395,471 (from NCBI)
The ZNF91 gene encodes a zinc finger protein of the KRAB (Kruppel-associated box) subfamily (Bellefroid et al., 1991 and Bellefroid et al., 1993).
The human genome is estimated to contain 300 to 700 zinc finger protein (ZNF) genes. ZNFs, which bind nucleic acids, perform many key functions, the most important of which is regulating transcription. The C2H2 ZNF family is characterized by repeated zinc finger motifs of approximately 28 amino acids that chelate a zinc ion using 2 cysteine residues and 2 histidine residues. The vast majority of these ZNFs are classified as Kruppel-like because they contain conserved 6-amino acid H/C links, the regions connecting successive finger repeats. About one-third of Kruppel-like ZNFs contain a conserved, approximately 75-amino acid motif, called the Kruppel-associated box (KRAB), in their N-terminal nonfinger region (Bellefroid et al., 1991). The KRAB is composed of 2 modules, the A box and the B box (summary by Bellefroid et al., 1993).
By screening a cDNA library derived from a human undifferentiated embryonal carcinoma cell line with the coding sequence of the ZNF85 (603899) N-terminal nonfinger region, which spans the KRAB domain, Bellefroid et al. (1991) isolated cDNAs encoding 11 distinct KRAB zinc finger proteins, including ZNF91, which they called HTF10.
Bellefroid et al. (1993) isolated a full-length human teratocarcinoma cell ZNF91 cDNA. It encodes a predicted 1,182-amino acid protein containing an N-terminal KRAB domain, which includes the KRAB A and KRAB B modules, and 35 contiguous finger repeats separated by Kruppel-like H/C link sequences. The KRAB domain and finger cluster are connected by a 92-amino acid spacer element that is conserved in a subset of KRAB zinc finger proteins; the authors stated that this spacer region defines the ZNF91 subfamily. By PCR, Bellefroid et al. (1993) identified cDNAs representing 2 additional ZNF91 mRNA isoforms, one of which encodes a deduced protein lacking the KRAB B module, and the other a protein lacking both the KRAB A and KRAB B modules. Northern blot analysis detected a 4.4-kb ZNF91 transcript in all human tissues tested, with the highest levels found in T-lymphoid cells.
Jacobs et al. (2014) reported that ZNF91 and ZNF93 (603975), 2 primate-specific KRAB zinc finger genes, evolved rapidly to repress the 2 distinct retrotransposon families SINE-VNTR-Alu (SVA) and long interspersed nuclear element-1 (LINE1) shortly after they began to spread in the human ancestral genome. ZNF91 underwent a series of structural changes 8 to 12 million years ago that enabled it to repress SVA elements. ZNF93 evolved earlier to repress the primate L1 lineage until about 12.5 million years ago, when the L1PA3 subfamily of retrotransposons escaped ZNF93's restriction through the removal of the ZNF93 binding site.
Bellefroid et al. (1993) determined that each KRAB module of ZNF91 is encoded by a separate exon, and the zinc finger domain by a single exon.
By somatic cell hybrid analysis and FISH, Bellefroid et al. (1993) mapped the ZNF91 gene to chromosome 19p13.1-p12. They found that most members of the ZNF91 gene family cluster in this region.
Bellefroid, E. J., Marine, J. C., Ried, T., Lecocq, P. J., Riviere, M., Amemiya, C., Poncelet, D. A., Coulie, P. G., de Jong, P., Szpirer, C., Ward, D. C., Martial, J. A. Clustered organization of homologous KRAB zinc-finger genes with enhanced expression in human T lymphoid cells. EMBO J. 12: 1363-1374, 1993. [PubMed: 8467795] [Full Text: https://doi.org/10.1002/j.1460-2075.1993.tb05781.x]
Bellefroid, E. J., Poncelet, D. A., Lecocq, P. J., Revelant, O., Martial, J. A. The evolutionarily conserved Kruppel-associated box domain defines a subfamily of eukaryotic multifingered proteins. Proc. Nat. Acad. Sci. 88: 3608-3612, 1991. [PubMed: 2023909] [Full Text: https://doi.org/10.1073/pnas.88.9.3608]
Jacobs, F. M. J., Greenberg, D., Nguyen, N., Haeussler, M., Ewing, A. D., Katzman, S., Paten, B., Salama, S. R., Haussler, D. An evolutionary arms race between KRAB zinc-finger genes ZNF91/93 and SVA/L1 retrotransposons. Nature 516: 242-245, 2014. [PubMed: 25274305] [Full Text: https://doi.org/10.1038/nature13760]