HGNC Approved Gene Symbol: PHF19
Cytogenetic location: 9q33.2 Genomic coordinates (GRCh38): 9:120,855,651-120,904,128 (from NCBI)
Wang et al. (2004) identified a novel gene, PHF19, near a retroviral integration site on chromosome 9 in an immortalized fibroblast line. Analysis of cDNA sequences derived from this gene indicated that it encoded a protein homologous to the Drosophila 'Polycomblike' (Pcl) protein. Wang et al. (2004) determined that the human gene, which they designated PCL3, encodes 2 deduced proteins: a short form (PCL3S) of 207 amino acids, and a long form (PCL3L) of 580 amino acids. The 2 proteins have 155 amino acids in common at their N termini. The PCL3L protein shares 41% and 44% sequence identity with human PCL1 (PHF1; 602881) and PCL2 (MTF2; 609882) proteins, respectively. The PCL family proteins contain a Tudor domain, 2 PHD fingers, a PCL homology domain, and a C-terminal tail. PCL3L also contains 2 putative nuclear localization signals. Northern blot analysis of multiple human tissues revealed expression of 2 major PCL3 transcripts of 1.0 and 4.8 kb at low levels in all tissues examined, with highest expression in thymus and heart. PCL3L was predominant in placenta, skeletal muscle, and kidney, and PCL3S was predominant in liver and peripheral blood leukocytes. Immunofluorescence microscopy revealed that PCL3S and PCL3L have distinct but overlapping localization patterns in the nucleus. A small amount of PCL3S was seen in the perinuclear cytoplasm.
In reporter gene assays, Wang et al. (2004) found that both PCL3S and PCL3L repressed transcriptional activity when fused to the binding domain of GAL4.
Using cDNA dot-blot and Northern blot analysis, Wang et al. (2004) found that PCL3 mRNA, especially that of PCL3S, was overexpressed in multiple cancers including colon, skin, lung, rectal, cervical, uterine, and liver cancers, as well as cell lines derived from melanomas and gliomas. A correlation between higher PCL3 expression and more advanced cancers was also observed, which led the authors to suggest that activation of PCL3 expression is not associated with a single step during tumor progression.
Pan et al. (2015) found that G9A (EHMT2; 604599) expression was unregulated in human pancreatic cancer cells and that upregulation of G9A increased methylation of H3K9 and H3K27 on the promoter of E-cadherin (CDH1; 192090) to downregulate its expression. Specifically, G9A bound directly to the promoter of PCL3, a component of polycomb repressive complex-2 (PRC2), and increased PCL3 expression. By increasing PCL3 expression, G9A increased recruitment of PRC2 to the E-cadherin promoter to downregulate its expression by repressing expression of KDM7A (619640). Bioinformatic analysis and in vivo study with mice supported these results and indicated that G9A likely orchestrated PCL3 and KDM7A to inhibit E-cadherin in pancreatic cancer.
Wang et al. (2004) determined that the PCL3 gene contains at least 15 exons and spans more than 20 kb of genomic DNA. Transcription of PCL3S stops at the end of exon 5, which contains a potential polyadenylation signal; in PCL3L, 101 nucleotides at the beginning of exon 5 are spliced to exon 6 and the sequence continues to the end of exon 15.
By sequence analysis, Wang et al. (2004) mapped the PCL3 gene to chromosome 9q33.3.
Pan, M.-R., Hsu, M.-C., Chen, L.-T., Hung, W.-C. G9a orchestrates PCL3 and KDM7A to promote histone H3K27 methylation. Sci. Rep. 5: 18709, 2015. [PubMed: 26688070] [Full Text: https://doi.org/10.1038/srep18709]
Wang, S., Robertson, G. P., Zhu, J. A novel human homologue of Drosophila polycomblike gene is up-regulated in multiple cancers. Gene 343: 69-78, 2004. [PubMed: 15563832] [Full Text: https://doi.org/10.1016/j.gene.2004.09.006]