Research topic: Structural and molecular mechanisms of ubiquitin signaling and chromatin modification; regulation of transcription
Protein function is dynamically regulated in the cell by reversible posttranslational modifications. We are interested in the mechanism by which chromatin modifications regulate transcription, nucleosome dynamics and the response to DNA damage. A particular focus is on the non-degradative signaling played by the attachment of the small protein, ubiquitin, to histone proteins.
We study the role that ubiquitination plays in these processes and on the mechanism of cross-talk between histone ubiquitination, acetylation and methylation, which together orchestrate the complex events underlying mRNA transcription and DNA repair. We use a combination of cryo-electron microscopy, x-ray crystallography, solution biochemistry, cell-based assays, and a variety of biophysical tools to gain insights into the mechanisms underlying these essential cellular processes.
Worden EJ, Zhang X, Wolberger C (2020) Structural basis for COMPASS recognition of an H2B-ubiquitinated nucleosome. Elife 9. pii: e53199. doi: 10.7554/eLife.53199.
Worden EJ, Hoffmann N, Wolberger C. (2019) Mechanism of cross-talk between H2B ubiquitination and H3 methylation by Dot1L. Cell, 176(6):1490-1501.
Nune M, Morgan MT, Connell Z, McCullough L, Jbara M, Sun H, Brik A, Formosa T, Wolberger C. (2019) FACT and Ubp10 collaborate to modulate H2B deubiquitination and nucleosome dynamics. eLife, pii: e40988. doi: 10.7554/eLife.40988
Morgan M, Haj-Yahya M, Ringel AE, Bandi P, Brik A, Wolberger C (2016) Structural basis for histone H2B deubiquitination by the SAGA DUB module. Science 351(6274): 725-8.
Ringel AE, Cieniewicz AM, Taverna SD, Wolberger C (2015) Nucleosome competition reveals processive acetylation by the SAGA HAT module. Proc Natl Acad Sci U S A 112(40):E5461-70.
Wiener W, DiBello AT, Lombardi PM, Guzzo CM, Zhang X, Maunis MJ, Wolberger C (2013) E2 ubiquitin conjugating enzymes regulate the deubiquitinating activity of OTUB1. Nature Structural and Molecular Biology 20(9):1033-9
Wiener R, Zhang X, Wang T, Wolberger C. (2012) The mechanism of OTUB1-mediated inhibition of ubiquitination. Nature 483: 618-22.