Sheila Teves
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sheilateves.bsky.social
Sheila Teves
@sheilateves.bsky.social
Assistant Professor, Biochemistry Department, Transcription & Chromatin biology, Outdoor enthusiast, Dog lover (otters too) 🇵🇭🇺🇲🇨🇦
Flung some discs, shared some laughs, and capped it off with good food. Summer vibes from the Teves lab!
June 12, 2025 at 3:07 AM
Vancouver showing pride
June 5, 2025 at 1:41 AM
The Teves lab totally glammed it up at the departmental holiday party!
December 20, 2024 at 12:15 AM
Sunshine and rainbows for the little dude
December 16, 2024 at 1:27 AM
Congratulations to recent PhD grad Dr. Thomas Nguyen @thomasfnguyen on wrapping up another research project!! 🎉🎉
Aided by co-authors Dr. James Kwan, grad student Hazel Cui, and undergrad Jennifer Mitchell.
An amazing team!
November 30, 2024 at 5:21 PM
We even found evidence for Pol III transcriptional memory during HS!
Prior HS altered Pol3's transcriptional response during subsequent stress.
HSF1 modulates this memory, ensuring rapid adaptation to recurring stress. Without HSF1, Pol III's response was disrupted
November 30, 2024 at 5:21 PM
But how? We looked at HSF1, the master regulator of HSPs.

Surprisingly, we found that it has no role in the initial downregulation, but is critical for Pol III recovery during HS. Hsf1-/- mESCs failed to restore Pol III activity by HS60.
November 30, 2024 at 5:21 PM
Using CUT&Tag, we found that Pol3 occupancy at tRNA genes decreases after 30 min of HS (HS30) but recovers after 60 min (HS60).

Confirmed by:
- analyzing published PRO-seq datasets in MEFS
- metabolic labeling using 5'BrU
November 30, 2024 at 5:21 PM
Beautiful Squamish mountains on the disc golf course
November 25, 2024 at 3:19 AM
Yay!
November 17, 2024 at 4:32 PM
Fall on the disc golf course
November 11, 2024 at 3:23 AM
A big surprise to us: despite their similarities, the homologs had vastly different DNA binding dynamics...

And these dynamics correlated with their molecular behavior
November 8, 2024 at 5:39 PM
How much of the molecular behaviour of the homologs is due to the divergent N-terminal domain?

Turns out, very little, at least under homeostasis. But removing the NTD of mouse TBP leads to exaggerated Pol2 response to heat shock, which is rescued by adding yeast NTD
November 8, 2024 at 5:38 PM
We confirmed our previous findings that mammalian RNA Pol II does not require TBP (or the homologs).

But no homolog fully rescued RNA Pol III transcription.

The most similar core domain to mouse TBP is the paralog TRF3. Yet, it has the least ability to bind DNA or rescue Pol3
Image
November 8, 2024 at 5:38 PM
Protein conservation also did not predict DNA binding ability, either at RNA Pol II gene promoters or tRNA genes
November 8, 2024 at 5:37 PM
We examined how TBP homologs have diverged in function by expressing homologs in mESCs while depleting the endogenous TBP.

Although the homologs share up to 85% similarity in sequence and predicted structure, none of the homologs we examined could rescue cell viability
Image
November 8, 2024 at 5:37 PM
TBP is central to initiation of the three main eukaryotic RNA Pols, and is highly conserved throughout evolution in both protein sequence and function.

Yet, recent studies have revealed that TBP homologs have diverged throughout evolution much more than previously thought.
November 8, 2024 at 5:36 PM
Happy Halloween from the Teves lab pH strip!
November 1, 2024 at 12:11 AM
Back to school for the Teves lab
September 27, 2024 at 10:02 PM
So what else?

We found that, during mitosis, TBP binds very strongly to rDNA promoters. Furthermore, restart of rDNA transcription following mitosis is impaired when TBP is depleted.

So... TBP seems to be bookmarking Pol1 genes!
July 3, 2024 at 2:54 PM
We then asked whether production of rRNAs are affected by TBP depletion. We pulsed the control and TBP depleted (IAA) cells with BrUTP, and measured new RNA production by RT-qPCR. We find little effect on Pol1 genes. Shown below are GAPDH and tRNA genes for Pol2 and Pol3 controls
July 3, 2024 at 2:53 PM
We first asked if TBP paralog (TRF2) compensates for TBP in Pol1 genes. Turns out, not so much.

So what happens to Pol1 binding? We performed CUT&Tag for TBP and Pol1 with and without TBP depletion (IAA), and find a slight impairment to Pol1 binding in gene bodies.
July 3, 2024 at 2:53 PM
Huge congratulations to the newly minted Dr. James Kwan and Dr. Thomas Nguyen!

These 2 students joined a brand new lab in 2018, went through the pandemic, and emerged as full-fledged scientists.

The first graduates of the Teves lab... a MAJOR milestone!
April 8, 2024 at 6:16 PM
A foggy sunrise makes for beautiful pictures
February 23, 2024 at 4:20 AM
February 23, 2024 at 4:19 AM