Tingting Yao Associate Professor

Office: Mrb 283

Phone: (970) 492-4116

Website: https://wp.natsci.colostate.edu/yaolab/

Google Scholar: https://scholar.google.com/citations?user=y4x3LGIAAAAJ&hl=en


  • Ph.D., University of Iowa


Our lab studies the interface between the ubiquitin-proteasome pathway and transcriptional regulation. Modification of components of the transcription machinery by ubiquitin can serve as a regulatory switch that both activate and limit gene expression. We are using a variety of biochemical and genetic approaches to define the molecular mechanisms that underlie these seemingly opposite processes. Ubiquitin (Ub) is a small protein of 76 amino acids. It is ubiquitous among all eukaryotes and it is highly conserved from yeast to man. The covalent attachment of Ub to other proteins, i.e., ubiquitination, is used as a regulatory signal in a broad spectrum of biological processes. These include targeting proteins for proteasomal degradation, intracellular trafficking, transcription activation, DNA damage repair, and chromatin remodeling. These different outcomes are due in part to the versatility of the Ub modification, which can vary in the number of Ub molecules attached and, if polyubiquitin chains are formed, the linkage between ubiquitins in the chain. Moreover, like phosphorylation, ubiquitination is reversible. Proteins are subject to ubiquitination and deubiquitination, and the balance between these competing processes determines the fate of the substrate. For most genes, transcription has long been regarded as the dominant regulatory process for production of a functional protein. Rather unexpectedly, recent discoveries have indicated that the Ub-proteasome pathway (UPP) is intimately involved in transcriptional regulation. Studies from many laboratories revealed that a variety of transcription activators are mono- or polyubiquitinated, and in some cases, their regulation involves a transition from one state to the other. Furthermore, although histones were among the first proteins found to be ubiquitinated, it was demonstrated only recently that ubiquitinated histone H2A is a hallmark of repressed chromatin, and that dynamic ubiquitination and deubiquitination of histone H2B is required for gene activation. An understanding of the mechanisms that link ubiquitination with transcription has been hindered by our very limited knowledge of the machinery that establishes and maintains specific (poly)Ub signals; moreover, the Ub receptors that recognize ubiquitinated transcription activators and histones are largely unknown. Our long-term interest is to understand how Ub and Ub-proteasome pathways interface with transcriptional regulation. Currently we are studying functions of a particularly interesting deubiquitinating enzyme called Uch37. We discovered that Uch37 is a shared subunit of both the proteasome and the INO80 chromatin remodeling complex, providing a unique link between these two processes. In addition, we are using a combination of genetics and proteomics approaches to identify new players at the crossroads of UPP and transcription. These studies will provide mechanistic insights into activation and inactivation of some of the most tightly controlled transcription factors, such as c-Myc and Estrogen Receptor α.


High-resolution and high-accuracy topographic and transcriptional maps of the nucleosome barrierZhijie Chen, Ronen Gabizon, Aidan I Brown, Antony Lee, Aixin Song, Cesar Diaz-Celis, Craig D Kaplan, Elena F Koslover, Tingting Yao* , Carlos Bustamante*eLife 8:e48281, 2019
High-affinity free ubiquitin sensors for quantifying ubiquitin homeostasis and deubiquitinationYun-Seok Choi, Sarah A. Bollinger, Luisa F. Prada, Francesco Scavone, Tingting Yao & Robert E. Cohen Nature Methods 16: 771–777, 2019
Nuclear condensates of the Polycomb protein chromobox 2 (CBX2) assemble through phase separationRoubina Tatavosian, Samantha Kent, Kyle Brown, Tingting Yao, Huy Nguyen Duc, Thao Ngoc Huynh, Chao Yu Zhen, Brian Ma, Haobin Wang, Xiaojun RenJournal of Biological Chemistry 294: 1451-1463., 2019
Recruitment and allosteric stimulation of a histone-deubiquitinating enzyme during heterochromatin assemblyAlexis Zukowski, Nouf Omar Al-Afaleq, Emily D Duncan, Tingting Yao, Aaron M JohnsonJournal of Biological Chemistry 293: 2498-2509, 2018
Live-cell single-molecule tracking reveals co-recognition of H3K27Me3 and DNA targets polycomb Cbx7-PRC1 to chromatinChao Yu Zhen, Roubina Tatavosian, Thao Ngoc Huynh, Huy Nguyen Duc, Raibatak Das, Marko Kokotovic, Jonathan B Grimm, Luke D Lavis, Jun Lee, Frances J Mejia, Yang Li, Tingting Yao, Xiaojun Ren Elife 5:e17667, 2016
Structural basis for the activation and inhibition of the UCH37 deubiquitylaseRyan T VanderLinden, Casey W Hemmis, Benjamin Schmitt, Ada Ndoja, Frank G Whitby, Howard Robinson, Robert E Cohen, Tingting Yao*, Christopher P Hill*Molecular Cell 57: 901-911., 2015
Generation of nonhydrolyzable ubiquitin–histone mimicsLindsey Long, MelonnieF urgason, Tingting YaoMethods 70: 134-8, 2014
The U4/U6 recycling factor SART3 has histone chaperone activity and associates with USP15 to regulate H2B deubiquitinationLindsey Long, Joseph P. Thelen, Melonnie Furgason, Mahmood Haj-Yahya, Ashraf Brik, Dongmei Cheng, Junmin Peng, Tingting YaoJournal of Biological Chemistry 289: 8916-30, 2014
Ubiquitin signals proteolysis-independent stripping of transcription factorsAda Ndoja, Robert E. Cohen, Tingting YaoMolecular Cell 53: 893-903, 2014
Structural insights into the assembly and function of the SAGA deubiquitinating moduleNadine L. Samara, Ajit B. Datta, Christopher E. Berndsen, Xiangbin Zhang, Tingting Yao, Robert E. Cohen, Cynthia WolbergerScience 328: 1025-9, 2010