Our lab studies how transcription is maintained and altered over time using the model system of mouse embryonic stem cells. Our research combines cutting-edge technologies including CRISPR/Cas9-mediated gene editing, genomics, and single molecule live-cell imaging to explore the mechanisms of transcriptional memory.
Our long term goal is to understand the mechanisms governing transcriptional memory over multiple time scales. By focusing on the underlying mechanisms, we hope to generate models for how cells maintain self-identity over time, how cells change their identity over time, and how the next generation of the organism is borne from the old. These important questions touch on the cornerstone of multi-cellularity and propagation.
Current Research Projects:
“A dynamic mode of mitotic bookmarking by transcription factors”
Each cell type in an organism has a specific function that is tied to its identity. Cell identity is determined primarily by the specific set of genes that are active in that cell type while silencing the rest. More importantly, the cell type specific gene program must be maintained throughout the lifetime of the organism.
This type of ‘transcriptional memory’ is potentially compromised every time a cell divides. When cells divide to form new cells, the DNA is condensed and gene activity is mostly turned off. However, each dividing cell also has to ‘remember’ the program of genes that specifies its identity. After division, how do the new daughter cells ‘know’ which genes to turn on and which ones to keep off?
One way that cells can regulate their genes is by using cell type specific transcription factors that can bind and regulate cell type specific target genes. Previous studies over the last 2 decades have shown that the transcription factors bound to DNA were all detached and become excluded from mitotic chromosomes during cell division, presenting a potential challenge to re-establishing the original gene program. Through studies in mouse embryonic stem cells that combined gene editing, genomics, and single molecule live cell imaging, we have shown that this finding is largely an artifact of the methods used to study the process. Movie 1 shows that the transcription factor Sox2 starts as highly enriched on mitotic chromosomes, but upon the addition of formaldehyde for fixation, most Sox2 molecules detach from DNA. In fact, many transcription factors still bind to and interact with DNA during cell division. This provides an efficient way for the newly formed cells to quickly reset to the pattern of gene activity appropriate for their cell type.
Prior to joining the UBC’s Biochemistry and Molecular Biology Department as an assistant professor, I was a postdoctoral fellow in Dr. Robert Tjian’s laboratory at the University of California, Berkeley. I received my Ph.D. from the University of Washington MCB program where I conducted graduate research with Dr. Steven Henikoff at the Fred Hutchinson Cancer Research Center.
My graduate research with Dr. Steven Henikoff explored how transcriptional regulation occurs in the context of chromatin. Funded by the National Science Foundation Graduate Research Fellowship Program, my work examined the question of how nucleosomes impact transcription and vice versa, and led to several publications as highlighted in my curriculum vitae, as well as the Harold M. Weintraub Graduate Student Award, a national award recognizing outstanding achievement during graduate studies in the biological sciences. During my postdoctoral training, I studied how transcription programs are maintained and regulated during the cell cycle as a fellow in Dr. Robert Tjian’s laboratory. This work, funded by the Jane Coffin Childs Postdoctoral Fellowship, has combined my expertise in genomics with cutting edge technologies on genome editing and live-cell imaging, with a focus on super-resolution single particle tracking, to challenge conventional wisdom on the mechanisms of transcription maintenance through mitosis.
Honours/Awards: (this information will appear on your public web profile)
2014 Jane Coffin Childs Foundation Postdoctoral Fellowship Award
2013 Harold M. Weintraub Graduate Student Award
2010 NSF Graduate Research Fellowship Award
2010 Best Poster Award. FASEB Conference: Transcriptional Regulation During Cell Growth, Differentiation and Development
2009 Honorable Mention, NSF GRF
2005 Post-Baccalaureate Cancer Research Training Award
2005 Magna Cum Laude
1. Teves SS*, An L, Bhargava-Shah A, Xie L, Darxacq X, and Tjian R. A stable mode of bookmarking by TBP recruits RNA Polymerase II to mitotic chromosomes. doi: https://doi.org/10.1101 /257451. Link
2. Teves SS, An L, Hansen AS, Xie L, Darzacq X, and Tjian R. A Dynamic Mode of Mitotic Bookmarking by Transcription Factors. eLife 2016;10.7554/eLife.22280. Link
3. Teves SS and Henikoff S. Transcription-generated DNA supercoils destabilize nucleosomes. Nat Struct Mol Biol. 2014; 21(1):88-94. Link
4. Teves SS, Henikoff S. DNA torsion as a feedback mediator of transcription and chromatin dynamics. Nucleus. 2014; 5(3):211-8. Link
5. Teves SS, Weber CM, Henikoff S. Transcription through the nucleosome. Trends Biochem Sci. 2014; 39(12):577-86. Link
Yang F, Teves SS, Kemp CJ, Henikoff S. Doxorubicin, DNA torsion, and chromatin dynamics. Biochim Biophys Acta Reviews. 2014 Jan;1845(1):84-9. doi: 10.1016 Link
6. Teves SS and Henikoff S. The heat shock response: a case study of chromatin dynamics in gene regulation. Biochem Cell Biol. 2013; 91(1):42-8. Link
7. Teves SS, Deal RB, and Henikoff S. Measuring Genome-Wide Nucleosome Turnover Using CATCH-IT. Methods Enzymol. 2012; 513:169-84 Link
8. Teves SS and Henikoff S. Salt fractionation of nucleosomes for genome-wide profiling. Methods Mol Biol. 2012; 833:421-32. Link
9. Teves SS and Henikoff S. Heat shock reduces stalled RNA polymerase II and nucleosome turnover genome-wide. Genes Dev. 2011; 25(22):2387-2397. Link
Conerly ML, Teves SS, Diolaiti D, Ulrich M, Eisenman RN and Henikoff S. Changes in H2A.Z occupancy and DNA methylation during B-cell lymphomagenesis. Genome Res. 2010; 20(10):1383-90. Link