Songtao Jia

Jia Lab Website

Epigenetic regulation of the genome.

Our laboratory is interested in the epigenetic control of genome organization, which involves heritable changes in gene function that do not involve changes in the DNA sequence. In eukaryotic cells, genomic DNA is packaged with histones into chromatin. Covalent modifications of histones, along with chromatin-remodeling and DNA modifications, are components of epigenetic mechanisms that help organize genomes into discrete domains that plays important regulatory roles in almost every aspect of DNA metabolism. These epigenetic mechanisms gradually restrict the developmental potential of stem cells during differentiation and also constitute “memories” of gene activity that ensure faithful inheritance of cell identity. Defects in epigenetic regulation have been extensively demonstrated to have causal roles in numerous developmental disorders and cancers.

Extensive efforts have been undertaken to identify new epigenetic histone modifications and the enzymes that catalyze these modifications. However, how histone-modifying activities are targeted to specific locations and how their activities are regulated is poorly understood. In addition, apart from a few well-known examples, how these modifications are inherited across generations is not clear. Using the fission yeast Schizosaccharomyces pombe as a model system, our laboratory combines biochemical, genetic, cytological, genomics and bioinformatics approaches to study these questions that provide molecular basis of gene silencing and epigenetic inheritance. We also use fission yeast and mammalian systems to study the molecular mechanisms by which the mis-regulation of histone modifying activities lead to human diseases and identify new pathways that can serve as therapeutic targets.

1. Toda, T., Fang, Y., Shan, C.M., Hua, X., Kim, J.K., Tang, L.C., Jovanovic, M., Tong, L., Qiao, F., Zhang, Z., and Jia, S.(2024). Mrc1 regulates parental histone segregation and heterochromatin inheritance. Molecular Cell S1097-2765(24)00573-2. doi:10.1016/j.molcel.2024.07.002. 
2. Fang, Y., Hua, X., Shan, C.-M., Toda, T., Qiao, F., Zhang, Z., and Jia, S. (2024). Coordination of histone chaperones for parental histone segregation and epigenetic inheritance. Genes & Development 38(3-4): 189-204. doi: 10.1101/gad.351278.123.
3. Yu, J., Zhang, Y., Fang, Y., Paulo, J.A., Yaghoubi, D., Hua, X., Shipkovenska, G., Toda, T., Zhang, Z., Gygi, S.P., Jia, S., Li, Q., and Moazed, D. (2024) A replisome-associated histone H3-H4 chaperone required for epigenetic inheritance. Cell S0092-8674(24)00766-9. doi: 10.1016/j.cell.2024.07.006.
4. Serra-Cardona, A., Hua, X., McNutt, S.W., Zhou, H., Toda, T., Jia, S., Chu, F., Zhang, Z. (2024). The PCNA-Pol complex couples lagging strand DNA synthesis to parental histone transfer for epigenetic inheritance. Sciences Advances 10(23):eadn5175. doi: 10.1126/sciadv.adn5175.
5. Giacomini, G., Piquet, S., Chevallier, O., Dabin, J., Bai, S.K., Kim, B., Siddaway, R., Raught, B., Coyaud, E., Shan, C.M., Reid, R., Toda, T., Rothstein, R., Barra, V., Wilhelm, T., Hamadat, S., Bertin, C., Crane, A., Dubois, F., Forne, I., Imhof, A., Bandopadhayay, P., Beroukhim, R., Naim, V., Jia, S., Hawkins, C., Rondinelli, B., and Polo, S.E. (2024). Aberrant DNA repair reveals a vulnerability in histone H3.3-mutant brain tumors. Nucleic Acids Research. 52(5):2372-2388. doi: 10.1093/nar/gkad1257.