Short Research Description
Epigenetic regulation of the genome.
Full Research Description
Our laboratory is interested in epigenetic control of genome organization, which allows for heritable changes in gene function that are not due to changes in the DNA sequence. In eukaryotic cells, genomic DNA is folded with histone and non-histone proteins in the form of chromatin. The building block of chromatin is the nucleosome, which contains 146 bp of DNA wrapped around an octamer of histones. Factors involved in covalent modifications of histones, together with chromatin-remodeling activities and DNA modifications, are components of intricate 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.
Recently, 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 the cellular machinery interprets these modifications to achieve diverse epigenetic states 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 epigenetic regulation. We also use fission yeast and mammalian systems to study the molecular mechanims by which the misregulation of histone modifying activities, such as by the oncogenic histone mutations, lead to human diseases and identify new pathways that can serve as therapeutic targets.
- Shan, C.M., Kim, J.K., Wang, J., Bao, K., Sun, Y., Chen, H., Yue, J.X., Stirpe, A., Zhang, Z., Lu, C., Schalch, T., Liti, G., Nagy, P.L., Tong, L., Qiao, F., and Jia, S. (2021). The histone H3K9M mutation synergizes with H3K14 ubiquitylation to selectively sequester histone H3K9 methyltransferase Clr4 at heterochromatin. Cell Rep. 35(7): 109137. doi:10.1016/j.elrep.2021.109137.
- Shan, C.M., Bao, K., Diedrich, J., Chen, X., Lu, C., Yates, J.R., and Jia, S. (2020). The INO80 complex regulates epigenetic inheritance of heterochromatin. Cell Rep. 33(13):108561. doi: 10.1016/j.celrep.2020.108561.
Bao, K., Shan, C.M., Moresco, J., Yates J., Jia, S. (2019). Anti-silencing factor Epe1 associates with SAGA to regulate transcription within heterochromatin. Genes Dev. 33(1-2):116-126.
Shan, C., Wang, J., Xu, K., Chen, H., Yue, J., Andrews, S., Moresco, J.J., Yates, J.R., Nagy, P.L., Tong, L., and Jia, S. (2016). A histone H3K9M mutation traps histone methyltransferase Clr4 to prevent heterochromatin spreading. Elife doi: 10.7554/elife.17903. Article
- Wang, J., Cohen, A.L., Letian, A., Tadeo, X., Moresco, J.J., Liu, J., Yates, J.R., Qiao, F., and Jia, S. (2016). The proper connection between shelterin components is required for telomeric heterochromatin assembly. Genes Dev. 30(7): 827-839. Article
- Wang, J., Reddy, B.D., and Jia, S. (2015). Rapid epigenetic adaptation to uncontrolled heterochromatin spreading. Elife doi:10.7554/elife.06179. Article
- Wang, J., Tadeo, X., Hou, H., Andrews, S., Moresco, J.J., Yates, J.R., Nagy, P.L., and Jia, S. (2014). Tls1 regulates splicing of shelterin components to control telomeric heterochromatin assembly and telomere length. Nucleic Acids Res. 42(18): 11419-32. Article
- Kallgren, S.P., Andrews, S., Tadeo, X., Hou, H., Moresco, J.J, Tu, P.G., Yates, J.R., Nagy, P., and Jia, S.(2014). The proper splicing of RNAi factors is critical for pericentric heterochromatin assembly in fission yeast. PLoS Genet. 10(5):e1004334. Article
- Tadeo, X., Wang, J., Kallgren, S.P., Liu, J., Reddy, B.D., Quio, F., and Jia, S. (2013). Elimination of shelterin components bypasses RNAi for pericentric heterochromatin assembly. Genes Dev. 27(22): 2489-99. Article
- Wang, J., Tadeo, X., Hou, H., Tu, P.G., Thompson, J., Yates, J.R., and Jia, S. (2013). Epe1 recruits BET family bromodomain protein Bdf2 to establish heterochromatin boundaries. Genes Dev. 27(17): 1886-902. Article
- Hou, H., Zhou, Z., Wang, Y., Wang, J., Kallgren, S.P., Kurchuk, T., Miller, E.A., Chang, F., and Jia, S.(2012) Csi1 links centromeres to the nuclear envelope for centromere clustering. J. Cell Biol. 199(5): 735-44. Article
- Reddy, B.D., Wang, Y., Niu, L., Higuchi, E.C., Marguerat, S.B., Bahler, J., Smith, G.R. and Jia, S. (2011) Elimination of a specific histone H3K14 acetyltransferase complex bypasses the RNAi pathway to regulate pericentric heterochromatin functions Genes. Dev 25(3): 214-219. Article
- Wang, Y., Reddy, B.D., Thompson, J., Wang, H., Noma, K., Yates, J.R. and Jia, S. (2009) Regulation of Set9-mediated H4K20 methylation by a PWWP domain protein. Mol. Cell 33(4): 428-437. Article
- Grewal, S.I. and Jia, S. (2007) Heterochromatin revisited Nature Review Genetics 8(1): 35-46. Article
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