Zu-Wen Sun, Ph.D.
Assistant Professor of Biochemistry
Vanderbilt University Medical Center
613C Light Hall, 23rd and Pierce
Nashville, TN 37232-0146
Histone Modifications, Chromatin Structure, and Gene Regulation
In eukaryotic cells, DNA is wrapped around octamers of histone proteins to form nucleosomes, the basic subunits of chromatin. Once considered an inert structure, it is now clear that chromatin plays an essential and dynamic role in regulating transcription, replication, recombination, and repair by dictating the accessibility of the underlying DNA template to various nuclear factors. Post-translational modifications of the histone proteins can result in heritable changes in gene expression without changes in DNA sequence, the actual genetic code. These epigenetic changes can cause stable oncogene activation or tumor-suppressor gene inactivation and have been shown to contribute to tumorigenesis. The mechanisms by which epigenetic imprints are established or maintained are still poorly understood. Many histone/chromatin modifiers are conserved from yeast to humans. In my laboratory, we use the budding yeast Saccharomyces cerevisiae as a powerful model system to identify new epigenetic regulators and to unravel the molecular mechanisms by which histone/chromatin-modifying enzymes affect chromatin structure and gene expression.
- Chandrasekharan, M. B., F. Huang and Z.-W. Sun "Decoding the trans-histone crosstalk: methods to analyze H2B ubiquitination, H3 methylation and their regulatory factors." Methods, 2011 Mar 7. [Epub ahead of print].
- Joo, H. Y., A. Jones, C. Yang, L. Zhai, A. D. Smith, Z. Zhang, M. B. Chandrasekharan, M. Renfrow, Z-W. Sun, Y. Wang, C. Chang and H. Wang. "Regulation of Histone H2A and H2B Deubiquitination and Xenopus Development by USP12 and USP46." J. Biol. Chem., 2867190-7201, 2011.
- Huang, F., M. B. Chandrasekharan, S. Bhaskara, S. W. Hiebert and Z.-W. Sun "The JmjN domain of Jhd2 is important for its protein stability and the plant homeodomain (PHD) finger mediates its chromatin association independent of H3K4 methylation." J. Biol. Chem., 28524548-24561, 2010 (Paper of the Week).
- Chandrasekharan, M. B., F. Huang and Z.-W. Sun "Histone H2B ubiquitination and beyond: Regulation of nucleosome stability, chromatin dynamics and the trans-histone H3 methylation." Epigenetics, 5460-468, 2010 (Cover article).
- Bhaskara, S., S. K. Knutson, G. Jiang, M. B. Chandrasekharan, A. Wilson, S. Zheng, A. Yenamandra, K. Loche, J.-L. Yuan, A. B. Summers, M. K. Washington, Z. Zhao, F. Wagner, Z-W. Sun, F. Xia, E. Holson, D. Khabele and S. W. Hiebert "Hdac3 is essential for the maintenance of chromatin structure and genome stability." Cancer Cell, 18436-447, 2010.
- Chandrasekharan, M. B., F. Huang, Y.-C. Chen and Z.-W. Sun "Histone H2B C-terminal helix mediates trans-histone H3K4 methylation independent of H2B ubiquitination." Mol. Cell. Biol., 303216-3232, 2010.
- Achame, E. M., E. Wassenaar, J. W. Hoogerbrugge, E. Sleddens-Linkels, M. Ooms, Z.-W. Sun, W. F. J. van IJcken, J. A. Grootegoed and W. M. Baarends "The ubiquitin-conjugating enzyme HR6B is required for maintenance of X chromosome silencing in mouse spermatocytes and spermatids." BMC Genomics, 11367, 2010.
- Nakanishi, S., J. S. Lee, K. E. Gardner, J. M. Gardner, Y.-H Takahashi, M. B. Chandrasekharan, Z.-W. Sun, M. A. Osley, B. D. Strahl, S. L. Jaspersen and A. Shilatifard "Histone H2BK123 monoubiquitination is the critical determinant for H3K4 and H3K79 trimethylation by COMPASS and Dot1." J. Cell Biol., 186371-377, 2009.
- Chandrasekharan, M., F. Huang and Z.-W. Sun "Ubiquitination of Histone H2B regulates chromatin dynamics by enhancing nucleosome stability." Proc. Natl. Acad. Sci. USA, 10616686-16691, 2009.
- Bhaskara, S., B. J. Chyla, J. M. Amann, S. K. Vanden-Eynden, D. Cortez, Z.-W. Sun and S. W. Hiebert "Deletion of Histone Deacetylase 3 reveals critical roles in S-phase progression and DNA damage control." Mol. Cell, 3061-72, 2008.
- Bradley, C., R. Meer, N. Roodi, H. Yan, M. Chandrasekharan, Z.-W. Sun, R. L. Mernaugh and F. F. Parl "Carcinogen-induced histone alteration in normal human mammary epithelial cells." Carcinogenesis, 282184-2192, 2007.
- Baarends, W. M., E. Wassenaar, J. W. Hoogerbrugge, S. Schoenmakers, Z.-W. Sun and J. A. Grootegoed "Increased H2AT120 phosphorylation and H3K4 dimethylation on the XY body in Hr6b knockout mouse spermatocytes is associated with derepession of the X chromosome in spermatids." J. Cell Sci., 1201841-1851, 2007.
- Freire-Picos, M. A., S. Krishnamurthy, Z.-W. Sun and M. Hampsey "Evidence that the Tfg1/Tfg2 dimer interface of TFIIF lies near the active center of the RNA polymerase II initiation complex." Nucleic Acids Res., 335045-5052, 2005.
- Xiao, T., C.-F. Kao, N.J. Krogan, Z.-W. Sun, J.F. Greenblatt, M.A. Osley and B.D. Strahl "Histone H2B ubiquitination is associated with elongating RNA Polymerase II." Mol. Cell. Biol., 25637-651, 2005.
- Linggi, B. E., S.J Brandt, Z.-W. Sun and S. W. Hiebert, SW "Translating the histone code into leukemia." J Cell Biochem, 96(5), 938-950, 2005.
- Daniel, J A., M. S. Torok, Z.-W. Sun, D. Schietz, C. D. Allis, J. R. Yates III and P. A. Grant "Deubiquitination of histone H2B by a yeast acetyltransferase complex regulates transcription." J. Biol. Chem., 279(3), 1867-1871, 2004.
- Briggs, S. D., T. Xiao, Z.-W. Sun, J. A. Caldwell, J. Shabanowitz, D. F. Hunt, C. D. Allis and B. D. Strahl "Gene silencing: trans-histone regulatory pathway in chromatin." Nature, 418498, 2002.
- Strahl, B. D., P. A. Grant, S. D. Briggs, Z.-W. Sun, J. R. Bone, J. A. Caldwell, S. Mollah, R. G. Cook, J. Shabanowitz, D. F. Hunt, and C. D. Allis "Set2 is a nucleosomal histone H3-specific methyltransferase that mediates transcriptional repression." Mol. Cell. Biol., 221298-1306, 2002.
- Sun, Z.-W. and C. D. Allis "Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast." Nature, 418104-108, 2002.
- Chen*, B.-S., Z.-W. Sun* and M. Hampsey "A Gal4-s54 Hybrid Protein that Functions as a Potent Activator of RNA Polymerase II Transcription in Yeast." J. Biol. Chem., 27623881-23887, 2001.
- Hsu*, J.-Y., Z.-W. Sun*, X. Li, M. Reuben, K. Tatchell, D. K. Bishop, J. M. Grushcow, C. J. Brame, J. A. Caldwell, D. F. Hunt, R. Lin, M. M. Smith, and C. D. Allis "Mitotic phosphorylation of histone H3 is governed by Ipl1/aurora kinase and Glc7/PP1 phosphatase in budding yeast and nematodes." Cell, 102279-291, 2000.
- Rea, S., F. Eisenhaber, D. O'Carroll, B. D. Strahl, Z.-W. Sun, M. Schmid, S. Opravil, K. Mechtler, C. P. Ponting, C. D. Allis, and T. Jenuwein "Regulation of chromatin structure by site-specific histone H3 methyltransferases." Nature (Article), 406593-599, 2000.
- Sun, Z.-W. and M. Hampsey "A general requirement for the Sin3-Rpd3 histone deacetylase complex in regulating silencing in Saccharomyces cerevisiae." Genetics, 152921-932, 1999.
- Zhang, Y., Z.-W. Sun, R. Iratni, H. Erdjument-Bromage, P. Tempst, M. Hampsey and D. Reinberg "SAP30, a novel protein conserved between human and yeast, is a critical component of a histone deacetylase complex." Mol. Cell, 11021-1031, 1998.
- Sun, Z.-W., A. Tessmer, and M. Hampsey "Functional interaction between TFIIB and the Rpb9 (Ssu73) subunit of RNA polymerase II in yeast." Nucleic Acids Res., 242560-2566, 1996.
- Sun, Z.-W. and M. Hampsey "Synthetic enhancement of a TFIIB defect by a mutation in SSU72, an essential yeast gene encoding a novel protein that affects transcription start site selection in vivo." Mol. Cell. Biol., 161557-1566, 1996.
- Sun, Z.-W. and M. Hampsey "Identification of the gene (SSU71/TFG1) encoding the largest subunit of TFIIF as a suppressor of a TFIIB mutation in Saccharomyces cerevisiae." Proc. Natl. Acad. Sci. USA, 923127-3131, 1995.