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PULSe Home > Faculty Members A-C > Scott Briggs
Scott D. Briggs
Current Research Interests:
Chromatin and histone modifications: In the eukaryotic cell, the precise organization and regulation of chromatin is critical for many cellular processes such as transcription, replication, recombination, repair, and chromosomal segregation. Although chromatin is defined as DNA associated with proteins, the fundamental repeating unit of chromatin is the nucleosome. The nucleosome consists of two copies of each core histone protein (H3, H4, H2A, and H2B) and 146 base pairs of DNA that wraps twice around them. Histone proteins contain a central histone-fold domain and N- and C-terminal tail domains that are subjected to extensive posttransitional modifications. Since posttransitional modifications on histones such as acetylation, phosphorylation, ubiquitination, and/or methylation can influence the chromatin environment and ultimately gene expression, we are interested in studying the enzymes and their associated proteins that mediate these modifications and how misregulation of these enzymes can lead to a disease state.
Histone methyltransferases and Cancer: Many SET domain-containing proteins have been associated with human cancers suggesting that they play an important regulatory roll in the cell. However, only a few have been identified as histone methyltransferases such as MLL1 and EZH2. Many of these SET domain-containing proteins are found either mutated, chromosomal translocated, or over-expressed when isolated from oncogenic cells. Therefore, we are interested in determining how mis-regulation and/or aberrant expression of these methyltransferases can lead to an oncogenic event and how aberrant histone methylation may play a role in oncogenesis
Selected Publications:
Mersman, D.P., Harmeyer, K.M., and Briggs, S.D. To be or NOT to be demethylated. Cell Cycle 8: 2135 - 2137, 2009.
Mersman, D. P., Du, H.N., Fingerman, I.M., South, P.F. and Briggs, S.D. Polyubiquitination of the demethylase Jhd2 controls histone methylation and gene expression. Genes & Development 23: 951-962, 2009.
Dhawan, R., Luo, H., Foerster, A.M., AbuQamar, S., Du, H.N., Briggs, S.D., Scheid, O.M., and Mengiste, T. HISTONE MONOUBIQUITINATION 1 interacts with a subunit of the mediator complex and regulates defense responses against necrotrophic fungal pathogens. Plant Cell 21:1000-1019, 2009.
Du, H.N., Fingerman, I.M. and Briggs, S.D. Histone H3 K36 methylation is mediated by a trans-histone methylation pathway involving an interaction between Set2 and histone H4. Genes & Development 22: 2786-2798, 2008.
Fingerman, I.M., Du, H.N., and Briggs, S.D. Controlling histone methylation via trans-histone pathways. Epigenetics 3: 237-242. 2008.
Fingerman, I.M., Du, H.N. and Briggs, S.D. Histone methyltransferase assays. Cold Spring Harbor (CSH) Protocols. doi:10.1101/pdb.prot4939, 2008.
Altaf, M., Utley, R.T., Lacoste, N., Tan, S., Briggs, S.D., and Côté, J. Interplay of chromatin modifiers on a short basic patch of histone H4 tail defines the boundary of telomeric heterochromatin. Molecular Cell. 28: 1002-1014, 2007.
Fingerman I.M., Li, H.C., and Briggs, S.D., A charge-based interaction between histone H4 and Dot1 is required for H3K79 methylation and telomere silencing: Identification of a new trans-histone pathway. Genes and Development. 21: 2018-2029, 2007.
Laribee, R.N., Shibata, Y., Mersman, D.P., Collins, S.R., Kemmeren, P., Weissman, J.S., Briggs, S.D., Krogan, N.J., Strahl, B.D. The proteasome links the CCR4/NOT complex to epigenetic regulation. PNAS. 104: 5836-5841, 2007.
Shi X., Kachirskaia I., Walter K.L., Kuo J.H., Lake A., Davrazou F., Chan S.M., Martin D.G., Fingerman I.M., Briggs S.D., Howe L., Utz P.J., Kutateladze T.G., Lugovskoy A.A., Bedford M.T., Gozani O. Proteome-wide analysis in S. cerevisiae identifies several PHD fingers as novel direct and selective binding modules of histone H3 methylated at either lysine 4 or lysine 36. J. Biol. Chem. 282: 2450-2455, 2007.
Bender, L.B., Suh, J., Carroll, C.R., Fong, Y, Fingerman, I.M., Briggs, S.D., Cao, R., Zhang, Y., Reinke, V. and Strome, S. MES-4, an autosome-associated histone methyltransferase that participates in silencing the X chromosomes in the C. elegans germ line. Development. 133: 3907-3917, 2006.
Fingerman, I.M., Wu, C-L., Wilson, B.D. and Briggs, S.D. Global loss of Set1-mediated H3 Lys4 trimethylation is associated with silencing defects in Saccharomyces cerevisiae. J. Biol. Chem. 280: 28761-28765, 2005.
Fingerman I.M. and Briggs S.D. p53-mediated transcriptional activation: from test tube to cell. Cell. 117: 690-691. 2004. (Preview).
Rice J.C., Briggs S.D., Ueberheide B., Barber C.M., Shabanowitz J., Hunt D.F., Shinkai Y. and Allis C.D. Mammalian histone methyltransferases direct different degrees of histone H3 lysine 9 methylation to define distinct domains of silent chromatin. Mol. Cell. 12: 1591-1598, 2003.
Milne T., Briggs S.D., Brock H.W., Martin M.E., Gibbs D., Allis C.D. and Hess J.L. MLL targets SET domain methyltransferase activity to Hox gene promoters. Mol. Cell. 10: 1107-1117, 2002.
Briggs S.D., Xiao T., Sun S.W., Caldwell J.A., Shabanowitz J., Hunt D.F., Allis C.D. and Strahl, B.D. Trans-histone regulatory pathway in chromatin. Nature. 418: 498, 2002.
Strahl B.D., Grant P.A., Briggs S.D., Sun Z.W., Bone J.R., Caldwell J.A., Mollah S., Cook R.G, Shabanowitz J., Hunt D.F., and Allis C.D. Set2 is a nucleosomal histone H3-selective methyltransferase that mediates transcriptional repression. Mol. Cell. Biol. 22: 1298-1306, 2002.
Briggs S.D., Bryk M., Strahl B.D., Cheung W.L., Davie J.K., Dent S.Y., Winston F., and Allis C.D. Histone H3 lysine 4 methylation is mediated by Set1 and required for cell growth and rDNA silencing in Saccharomyces cerevisiae. Genes and Development 15: 3286-3295, 2001.
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