Sheila Teves

Enhancer-promoter compatibility is mediated by the promoter-proximal region Gene promoters induce transcription in response to distal enhancers. How enhancers specifically activate their target promoter while bypassing other promoters remains unclear. Here, we find that the p...

What is a promoter? And how does it work?

We very happy to share our latest work trying to understand enhancer-promoter compatibility.
I am very excited about the results of @blanka-majchrzycka.bsky.social, which changed the way I think about promoters

www.biorxiv.org/content/10.1...

Thanks! Big shoutout to Hazel Cui who led this study and will defend her PhD this year!

Molecular determinants underlying functional divergence of TBP homologs The TATA-box binding protein (TBP) is a highly conserved basal transcription factor and a core component of the pre-initiation complex (PIC) for all three eukaryotic RNA polymerases (RNA Pols). Despit...

How does a “universal” transcription factor evolve to do species-specific jobs?
Our new preprint reveals how divergence in TBP’s domains shapes transcriptional specialization across eukaryotes.

Read it here 👉

www.biorxiv.org/content/10.1...

#MolecularEvolution #Transcription

Flung some discs, shared some laughs, and capped it off with good food. Summer vibes from the Teves lab!

Vancouver showing pride

So excited to see this work out in
@narjournal.bsky.social

academic.oup.com/nar/article/...

Congratulations to Hazel Cui on outstanding work!

Keep an eye out for part 2 of this project 😎

In #GENETICS, @sheilateves.bsky.social et al. study the regulation of Pol III transcription during different stages of heat shock stress in mouse embryonic stem cells, showing that the dynamic regulation & recovery of Pol III may be exclusive to the heat shock response.

Read more: buff.ly/s966iZ1

From what we can measure, it affects all tRNA genes! The recovery from HS is a really interesting question

Definitely a great experience with Genetics!

So proud of Thomas Nguyen and co-authors on the publication of this manuscript. Now out in Genetics!

See full paper here! academic.oup.com/genetics/adv...

Thank you to the editors of Genetics for effiecient handling, and to the peer reviewers for excellent feedback

Really fun chatting with JP, Enya, and Lawrence!

The Teves lab totally glammed it up at the departmental holiday party!

EXTRA-seq: a genome-integrated extended massively parallel reporter assay to quantify enhancer-promoter communication Precise control of gene expression is essential for cellular function, but the mechanisms by which enhancers communicate with promoters to coordinate this process are not fully understood. While seque...

Finally out! We present EXTRA-seq, a new EXTended Reporter Assay to quantify endogenous enhancer-promoter communication at kb scale!
www.biorxiv.org/content/10.1...
A 🧵about what it can do:
#SynBio #DeepLearning #GeneRegulation

Sunshine and rainbows for the little dude

Ever wondered how transcription choreographs histone modifications? Our work reveals the basis of co-transcriptional H3K36me3 by SETD2. We visualize how a histone writer coordinates with the transcription machinery! This is the magnus opus of @jonmarkert.bsky.social!
tinyurl.com/setd2

Pol II degradation activates cell death independently from the loss of transcription Pol II-mediated transcription is essential for eukaryotic life. While loss of transcription is thought to be universally lethal, the associated mechanisms promoting cell death are not yet known. Here,...

We just posted a preprint about a death mechanism that we find truly surprising.

When you turn off transcription, cells die (duh!)... but did you know this happens due to loss of Pol II itself, not loss of Pol II activity!?!

preprint here and a thread (1/n): www.biorxiv.org/content/10.1...
🧪

🎄🔔Ho Ho ho!😆 Our final
#FragileNucleosome
seminar of the year! We are excited to host Julia and Nithya, two amazing ECR scientists!
🗓️Don't forget to register: us06web.zoom.us/webinar/regi...

Women faculty feel ‘pushed’ from academia by poor workplace climate The gender gap in faculty attrition worsens after tenure, according to a new study

"Women full professors are 19% more likely than men at the same career stage to leave academia, as compared with 6% for women assistant professors and 10% for associates."

Chromatin Compaction Follows a Power Law Scaling with Cell Size from Interphase Through Mitosis Coordination of mitotic chromosome compaction with cell size is crucial for proper genome segregation during mitosis. During development, DNA content remains constant but cell size evolves, necessitat...

1/ One more preprint before the holidays! In which we find that chromatin compaction scales with cell size from interphase through mitosis. A collaboration from waaay back (see end of thread) with Melike Lakadamyali @melikel.bsky.social and Jerome Solon. A thread: 👇
www.biorxiv.org/content/10.1...

DNA hypomethylation promotes UHRF1-and SUV39H1/H2-dependent crosstalk between H3K18ub and H3K9me3 to reinforce heterochromatin states Liu et al. report that DNMT1 inhibition causes transient accumulation of hemi-methylated DNA at CpG islands, which stimulates UHRF1-mediated H3K18ub. This enhances SUV39H1/H2 activity, nucleates new H...

Thrilled to share a new study from the lab revealing an H3K18ub-H3K9me3 crosstalk mechanism, roles for UHRF1 and its E3 ligase activity in regulating a hierarchy of repressive histone methylation signaling, and a strategy for targeting SUV39H1/H2 to improve DNMT1 inhibitor efficacy! #epigenetics

🙏

We designed MS2 and PP7 binding coat proteins that are degraded in cells except when bound by their hairpin RNAs.

You can check out our pre-print here: tinyurl.com/27p7hyt9,
and listen to a Google AI-generated podcast on it here: notebooklm.google.com/notebook/d71...

Yeah, we’ve been using Cut&Tag for TFs for years now… seems fine for some but not others 🤷‍♀️

🙏

All editors rely on Pol3 because we use its promoters to transcribe the gRNA from plasmid vectors.
I never thought something so cell-essential would be regulated.
-> food for thought wrt editing cell types in various states.

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!

Dynamic Pol3 regulation highlights a potential mechanism for prioritizing resources during stress. HSF1’s role bridges Pol II & Pol III transcription, underscoring its critical function in global stress adaptation.

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

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.

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