How do sarcomeric mutations disrupt the transition to adult cardiac metabolism? Our study in TNNT2-linked HCM hiPSC-CMs reveals an early energetic deficit, paradoxical mTORC1 suppression, and a pathway to therapeutic rescue. Congrats to Homa Hamledari and the team! www.biorxiv.org/content/10.1...

Molecular Rewiring in TNNT2-Linked Hypertrophic Cardiomyopathy hiPSC-Derived Cardiomyocytes upon Metabolic Maturation

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are widely used to model cardiac development and inherited cardiomyopathies, yet their immature metabolic state limits interpreta...

biorxiv.org

Congratulations to Homa on an exceptional PhD thesis defense! Homa is co-supervised between me and the late Dr. Glen Tibbits, who would have been so proud of Homa's accomplishments. Welcome Dr. Homa Hamledari!

Congratulations to 2 Teves lab graduate students successfully defending their PhDs!!

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...

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...

biorxiv.org

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

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...

biorxiv.org

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 😎

Sheila Teves@sheilateves.bsky.social · 2y ago

Latest research from the Teves lab is now out on Biorxiv! "Functional divergence of TBP homologs through distinct DNA binding dynamics" biorxiv.org/content/10.1... Here, we examine how conservation is balanced with diversification throughout evolution, using TBP as a case study.

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

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

Dynamic regulation of murine RNA polymerase III transcription during heat shock stress

Abstract. Cells respond to many different types of stresses by overhauling gene expression patterns, both at the transcriptional and translational levels.

academic.oup.com

Sheila Teves@sheilateves.bsky.social · 2y ago

🎉Excited to share our new preprint on Biorxiv 🥳 We uncover how RNA Polymerase III (Pol3) dynamically regulates tRNA transcription during heat shock (HS) stress! So what did we find? 🧵 www.biorxiv.org/content/10.1...

Really fun chatting with JP, Enya, and Lawrence!

jp flores (he/him)@jpflores.rbind.io · 2y ago

In this episode, I interviewed Dr. Sheila Teves (@sheilateves.bsky.social) and Dr. Lawrence David (Duke) with a fellow graduate student at Duke, Enya (@erd2.bsky.social)! Words cannot explain how fun it was chatting with other Filipino scientists 😊🇵🇭 #representationmatters

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

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

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...

biorxiv.org

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

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... 🧪

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,...

biorxiv.org

🎄🔔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 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."

Women faculty feel ‘pushed’ from academia by poor workplace climate

The gender gap in faculty attrition worsens after tenure, according to a new study

science.org

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...

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...

biorxiv.org

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

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...

cell.com

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...

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.

Sheila Teves@sheilateves.bsky.social · 2y ago

🎉Excited to share our new preprint on Biorxiv 🥳 We uncover how RNA Polymerase III (Pol3) dynamically regulates tRNA transcription during heat shock (HS) stress! So what did we find? 🧵 www.biorxiv.org/content/10.1...

🎉Excited to share our new preprint on Biorxiv 🥳 We uncover how RNA Polymerase III (Pol3) dynamically regulates tRNA transcription during heat shock (HS) stress! So what did we find? 🧵 www.biorxiv.org/content/10.1...

Dynamic regulation of RNA Polymerase III transcription in mouse embryonic stem cells during heat shock stress

Cells respond to many different types of stresses by overhauling gene expression patterns, both at the transcriptional and translational level. Under heat stress, global transcription and translation ...

biorxiv.org

Very interesting paper from @mitchguttman.bsky.social previously in @biorxivpreprint.bsky.social out in Nature Genetics. "ChIP-DIP generates context-specific protein localization maps at consortium scale" www.nature.com/articles/s41...

ChIP-DIP maps binding of hundreds of proteins to DNA simultaneously and identifies diverse gene regulatory elements - Nature Genetics

ChIP-DIP (ChIP done in parallel) is a highly multiplex assay for protein–DNA binding, scalable to hundreds of proteins including modified histones, chromatin regulators and transcription factors, offe...

nature.com

Machine-guided design of cell-type-targeting cis-regulatory elements www.nature.com/articles/s41... @natureportfolio.bsky.social

Machine-guided design of cell-type-targeting cis-regulatory elements - Nature

A generalizable framework to prospectively engineer cis-regulatory elements from massively parallel reporter assay models can be used to write fit-for-purpose regulatory code.

nature.com

Beautiful Squamish mountains on the disc golf course

The strain on scientific publishing: we set out to characterise the remarkable growth of the scientific literature in the last few years, in spite of declining growth in total scientists. What is going on? direct.mit.edu/qss/article/... A 🧵 1/n #AcademicSky #PhDchat #ScientificPublishing #SciPub

(1/n) What better way to start posting on Bluesky than to share our recent preprint, in collaboration with @timhughesto.bsky.social, on characterization of the intrinsic DNA binding specificities of 179 human transcription factors using a new assay, GHT-SELEX: www.biorxiv.org/content/10.1...

GHT-SELEX demonstrates unexpectedly high intrinsic sequence specificity and complex DNA binding of many human transcription factors

A long-standing challenge in human regulatory genomics is that transcription factor (TF) DNA-binding motifs are short and degenerate, while the genome is large. Motif scans therefore produce many fals...

biorxiv.org

Hey new and seasoned BlueSkeeters! For our next #FragileNucleosome seminar session, we are happy to host another three amazing ECR scientists: Sanne, Vivek and Thomas! 🗓️Don't forget to register: us06web.zoom.us/webinar/regi...

If this exists already.. I feel you can never have too many pet packs. Please let me know if you'de like to join. go.bsky.app/4TA4G8D