TCF19 Promotes Cell Proliferation through Binding to the Histone H3K4me3 Mark

• Published in: Biochemistry (Easton) 2020-02, Vol.59 (4), p.389-399
• Main Authors: Mondal, Payel, Sen, Sabyasachi, Klein, Brianna J, Tiwary, Niharika, Gadad, Shrikanth S, Kutateladze, Tatiana G, Roy, Siddhartha, Das, Chandrima
• Format: Article
• Language: English
• Subjects: Carcinoma, Hepatocellular - metabolism; Cell Line, Tumor; Cell Proliferation - physiology; DNA-Binding Proteins - metabolism; Hep G2 Cells; Histone Code; Histones - genetics; Histones - metabolism; Humans; Liver Neoplasms - metabolism; Lysine - metabolism; Methylation; Models, Molecular; PHD Zinc Fingers - physiology; Protein Binding; Transcription Factors - metabolism; Transcription Factors - physiology
• ISSN: 0006-2960; 1520-4995; 1520-4995
• DOI: 10.1021/acs.biochem.9b00771

Transcription factor 19 (TCF19) plays critical roles in type 1 diabetes and the maintenance of pancreatic β cells. Recent studies have also implicated TCF19 in cell proliferation of hepatic carcinoma and non-small cell lung carcinoma; however, the mechanism underlying this regulation remains elusive. At the molecular level, TCF19 contains two modules, the plant homeodomain (PHD) finger and the forkhead-associated (FHA) domain, of unclear function. Here, we show that TCF19 mediates hepatocellular carcinoma HepG2 cell proliferation through its PHD finger that recognizes trimethylated lysine 4 of histone 3 (H3K4me3). W316 of the PHD finger of TCF19 is one of the critical residues eliciting this function. Whole genome microarray analysis and orthogonal cell-based assays identified a large subset of genes involved in cell survival and proliferation that depend on TCF19. Our data suggest that TCF19 acts as a pro-oncogene in hepatocellular carcinoma cells and that its functional PHD finger is critical in cell proliferation.