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Songtao Jia
Associate Professor
National Academies Education Fellow in the Life Sciences
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. Advantages of fission yeast include highly conserved histone modifications, simple genome organization, a completely sequenced genome, and amenability to genetic and biochemical manipulations. All of these offer unprecedented opportunities for assessing the role of histone modification in the epigenetic regulation of the genome, which is essential to our understanding of stem cell and cancer biology.
Representative Recent Publications
  • 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
  • Hou, H., Wang, Y., Kallgren, S.P., Thompson, J., Yates, J.R. and Jia, S. (2010) Histone variant H2A.Z regulates centromere silencing and chromosome segregation in fission yeast J. Biol. Chem 285(3): 1909-1918. Article
  • Wang, Y. and Jia, S. (2009) Degrees make all the difference: the multifunctionality of histone H4 lysine 20 methylation. Epigenetics 4(5): 1-4. 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
  • Jia, S., Kobayashi, R., and Grewal, S.I. (2005) Ubiquitin ligase component Cul4 associates with Clr4 histone methyltransferase to assemble heterochromatin Nature Cell Biology 7(10): 1007-1013. Article
  • Jia, S., Yamada, T. and Grewal S.I. (2004) Heterochromatin regulates cell type-specific long-range chromatin interactions essential for directed recombination Cell 119(4): 469-80. Article
  • Jia, S., Noma, K. and Grewal, S.I. (2004) RNAi- independent heterochromatin nucleation by the stress-activated ATF/ CREB family proteins. Science 304(5679): 1971-6. Article
  • Verdel, A., Jia, S., Gerber, S., Sugiyama, T., Gygi, S., Grewal, S.I. and Moazed, D (2004) RNAi-mediated targeting of heterochromatin by the RITS complex. Science 303(5658): 672-6. Article
Songtao Jia
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