Tcf20, also known as Transcription co-activator factor 20, encodes a nuclear chromatin-binding protein involved in the regulation of gene expression. It is a regulator of transcription factors related to extracellular matrix remodelling and is part of a chromatin complex that includes MeCP2, RAI1, PHF14, and HMG20A, playing a vital role in epigenetic and transcriptional regulation [1,4].

In mouse models, Tcf20 deficiency leads to multiple consequences. Tcf20 knockout (Tcf20-/-) newborn mice show impaired neural development and death after birth. Heterozygous mice display higher CCl4-induced liver fibrosis, differential expression of genes related to extracellular matrix homeostasis, and abnormal behavioural patterns similar to autism-like phenotypes. Tcf20-/-embryonic livers and mouse embryonic fibroblast (MEF) cells have differential expression of mitochondrial oxidative phosphorylation chain structural proteins, increased mitochondrial metabolic activity, and altered citric acid cycle metabolites. These findings parallel those in humans with TCF20 pathogenic variants, such as fibrosis score alterations and elevated plasma succinate concentration [2]. Tcf20 deletion in mice significantly reduces the number of neurons, impairing neurogenesis and causing abnormal brain functions. Transcriptome and ChIP-qPCR analyses show that the DNA demethylation factor TDG is a downstream target gene of Tcf20, and TDG affects T-cell factor 4 (TCF-4) expression to modulate neural differentiation. Overexpression of TDG or TCF-4 can rescue the deficient neurogenesis of TCF20 knockdown brains [3].

In conclusion, Tcf20 is essential for multiple biological processes. Its functions span across neural development, liver fibrogenesis, and mitochondrial metabolism. Mouse models, especially gene knockout models, have been crucial in revealing its role in these processes and in understanding the associated neurodevelopmental disorders, liver fibrosis, and metabolic disruptions [2,3].