The Lewis Lab
@peterlewislab.bsky.social
Chromatin biochemistry and genomics in development and cancer. UW-Madison School of Medicine and Public Health
TheLewisLab.net
TheLewisLab.net
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The Lewis Lab
@peterlewislab.bsky.social
· Jul 23
We are excited to share our new preprint demonstrating that nucleic acid interactions with SUZ12 constrain PRC2 activity, establishing a kinetic buffer essential for targeted gene silencing and revealing vulnerabilities in diffuse midline gliomas.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Reposted by The Lewis Lab
New work from Tahirov x Lim collaboration! @qixianghe.bsky.social from my lab contributed the cryo-EM structures for this work. We are excited to help explain how anti-HSV drugs work and to guide their future development.
www.science.org/doi/10.1126/...
@unmc.bsky.social @uwbiochem.bsky.social
www.science.org/doi/10.1126/...
@unmc.bsky.social @uwbiochem.bsky.social
Structural basis of herpesvirus helicase-primase inhibition by pritelivir and amenamevir
Structural studies of HSV-1 helicase-primase revealed how pritelivir and amenamevir bind and block its helicase activity.
www.science.org
November 10, 2025 at 12:14 AM
New work from Tahirov x Lim collaboration! @qixianghe.bsky.social from my lab contributed the cryo-EM structures for this work. We are excited to help explain how anti-HSV drugs work and to guide their future development.
www.science.org/doi/10.1126/...
@unmc.bsky.social @uwbiochem.bsky.social
www.science.org/doi/10.1126/...
@unmc.bsky.social @uwbiochem.bsky.social
Reposted by The Lewis Lab
1/ 🚀 AEBP2 isn’t what we thought.
You were told that AEBP2 promotes PRC2 activity on chromatin.
We found the opposite: the most prevalent AEBP2 isoform inhibits PRC2 activity.
👉 surl.li/cgwqcq
A thread 🧵
You were told that AEBP2 promotes PRC2 activity on chromatin.
We found the opposite: the most prevalent AEBP2 isoform inhibits PRC2 activity.
👉 surl.li/cgwqcq
A thread 🧵
October 31, 2025 at 10:53 AM
1/ 🚀 AEBP2 isn’t what we thought.
You were told that AEBP2 promotes PRC2 activity on chromatin.
We found the opposite: the most prevalent AEBP2 isoform inhibits PRC2 activity.
👉 surl.li/cgwqcq
A thread 🧵
You were told that AEBP2 promotes PRC2 activity on chromatin.
We found the opposite: the most prevalent AEBP2 isoform inhibits PRC2 activity.
👉 surl.li/cgwqcq
A thread 🧵
Reposted by The Lewis Lab
Our paper in Science is out! @souravagrawal.bsky.social, @rlynn.bsky.social, @susvirkar.bsky.social, and the rest of the team show human RPA is a telomerase processivity factor essential for telomere maintenance. This reshapes our thinking about telomerase regulation. www.science.org/doi/10.1126/...
Human RPA is an essential telomerase processivity factor for maintaining telomeres
Telomerase counteracts telomere shortening by repeatedly adding DNA repeats to chromosome ends. We identified the replication protein A (RPA) heterotrimer as a telomerase processivity factor critical ...
www.science.org
October 30, 2025 at 10:07 PM
Our paper in Science is out! @souravagrawal.bsky.social, @rlynn.bsky.social, @susvirkar.bsky.social, and the rest of the team show human RPA is a telomerase processivity factor essential for telomere maintenance. This reshapes our thinking about telomerase regulation. www.science.org/doi/10.1126/...
Reposted by The Lewis Lab
Now out in Science! Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle. In @vcushing.bsky.social's magnum opus, we use #cryoEM to figure out how the CDK-activating kinase recognises CDKs to fully activate them - a key step in cell cycle control.
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Structural basis of T-loop–independent recognition and activation of CDKs by the CDK-activating kinase
Cyclin-dependent kinases (CDKs) are prototypical regulators of the cell cycle. The CDK-activating kinase (CAK) acts as a master regulator of CDK activity by catalyzing the activating phosphorylation o...
www.science.org
October 16, 2025 at 7:17 PM
Now out in Science! Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle. In @vcushing.bsky.social's magnum opus, we use #cryoEM to figure out how the CDK-activating kinase recognises CDKs to fully activate them - a key step in cell cycle control.
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Reposted by The Lewis Lab
Today I am so pleased to present our work on how chromatin remodelers affect mesoscale chromatin organization.
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
ATP-dependent remodeling of chromatin condensates reveals distinct mesoscale outcomes
Adenosine triphosphate (ATP)–dependent chromatin remodeling enzymes mobilize nucleosomes, but how such mobilization affects chromatin condensation is unclear. We investigate effects of two major remod...
www.science.org
October 2, 2025 at 10:55 PM
Today I am so pleased to present our work on how chromatin remodelers affect mesoscale chromatin organization.
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Reposted by The Lewis Lab
How do flexible regions of histone chaperones team up to handle histones? Together with Fred Winston’s lab
@harvardmed.bsky.social, we reveal new insights in our study just out in Mol Cell. Hats off to James Warner and Vanda Lux @iocbprague.bsky.social for their key contributions! dlvr.it/TNB145
@harvardmed.bsky.social, we reveal new insights in our study just out in Mol Cell. Hats off to James Warner and Vanda Lux @iocbprague.bsky.social for their key contributions! dlvr.it/TNB145
September 21, 2025 at 7:31 PM
How do flexible regions of histone chaperones team up to handle histones? Together with Fred Winston’s lab
@harvardmed.bsky.social, we reveal new insights in our study just out in Mol Cell. Hats off to James Warner and Vanda Lux @iocbprague.bsky.social for their key contributions! dlvr.it/TNB145
@harvardmed.bsky.social, we reveal new insights in our study just out in Mol Cell. Hats off to James Warner and Vanda Lux @iocbprague.bsky.social for their key contributions! dlvr.it/TNB145
Reposted by The Lewis Lab
Requirements for establishment and epigenetic stability of mammalian heterochromatin.
www.cell.com/molecular-ce...
www.cell.com/molecular-ce...
Requirements for establishment and epigenetic stability of mammalian heterochromatin
Tatarakis et al. study how H3K9me3 heterochromatin is formed and inherited in mammalian
cells. Using a synthetic heterochromatin assembly system and genetic screens, they
uncover requirements for init...
www.cell.com
September 21, 2025 at 10:44 PM
Requirements for establishment and epigenetic stability of mammalian heterochromatin.
www.cell.com/molecular-ce...
www.cell.com/molecular-ce...
Reposted by The Lewis Lab
Some (+)ve news to lighten another heavy weekend: our latest preprint (c/o Mattiroli + Ramani labs) is up!
www.biorxiv.org/content/10.1...
A tour-de-force by 1st authors Bruna Eckhardt & @palindromephd.bsky.social, focusing on chromatin replication. RTs welcome; tweetorial in 3,2...(1/n)
www.biorxiv.org/content/10.1...
A tour-de-force by 1st authors Bruna Eckhardt & @palindromephd.bsky.social, focusing on chromatin replication. RTs welcome; tweetorial in 3,2...(1/n)
The eukaryotic replisome intrinsically generates asymmetric daughter chromatin fibers
DNA replication is molecularly asymmetric, due to distinct mechanisms for lagging and leading strand DNA synthesis. Whether chromatin assembly on newly replicated strands is also asymmetric remains un...
www.biorxiv.org
September 20, 2025 at 4:10 PM
Some (+)ve news to lighten another heavy weekend: our latest preprint (c/o Mattiroli + Ramani labs) is up!
www.biorxiv.org/content/10.1...
A tour-de-force by 1st authors Bruna Eckhardt & @palindromephd.bsky.social, focusing on chromatin replication. RTs welcome; tweetorial in 3,2...(1/n)
www.biorxiv.org/content/10.1...
A tour-de-force by 1st authors Bruna Eckhardt & @palindromephd.bsky.social, focusing on chromatin replication. RTs welcome; tweetorial in 3,2...(1/n)
Reposted by The Lewis Lab
Thrilled that our work is now finally out in Nature Comms!
rdcu.be/eG3vP
We reveal cryo-EM structures of the MRN complex bound to DNA & TRF2 - showing how DNA breaks are sensed and regulated at telomeres.
Fantastic work by first authors @yilanfan.bsky.social @filizkuybu.bsky.social & Hengjun!
rdcu.be/eG3vP
We reveal cryo-EM structures of the MRN complex bound to DNA & TRF2 - showing how DNA breaks are sensed and regulated at telomeres.
Fantastic work by first authors @yilanfan.bsky.social @filizkuybu.bsky.social & Hengjun!
September 18, 2025 at 4:09 PM
Thrilled that our work is now finally out in Nature Comms!
rdcu.be/eG3vP
We reveal cryo-EM structures of the MRN complex bound to DNA & TRF2 - showing how DNA breaks are sensed and regulated at telomeres.
Fantastic work by first authors @yilanfan.bsky.social @filizkuybu.bsky.social & Hengjun!
rdcu.be/eG3vP
We reveal cryo-EM structures of the MRN complex bound to DNA & TRF2 - showing how DNA breaks are sensed and regulated at telomeres.
Fantastic work by first authors @yilanfan.bsky.social @filizkuybu.bsky.social & Hengjun!
Reposted by The Lewis Lab
Very interesting new @wbickmor.bsky.social commentary on the mechanistic mystery that is very distal enhancer-promoter interactions www.nature.com/articles/s41...
Is enhancer-driven gene regulation all wrapped up? - Nature Reviews Genetics
In this Comment, Wendy Bickmore discusses mechanistic models of how 3D genome organization facilitates communication between distant enhancers and their target promoters to regulate gene expression.
www.nature.com
September 17, 2025 at 12:41 PM
Very interesting new @wbickmor.bsky.social commentary on the mechanistic mystery that is very distal enhancer-promoter interactions www.nature.com/articles/s41...
Reposted by The Lewis Lab
Very excited to share an excellent review from @teresa-urli.bsky.social, published one week before her PhD defense! We did a deep dive into the fascinating biology of the variant Polycomb complex, PRC1.6 (1/5) journals.plos.org/plosgenetics...
Epigenetic relay: Polycomb-directed DNA methylation in mammalian development
In mammals, repression of germline-specific gene expression is essential for preserving somatic cell identity and preventing disease. Germline gene silencing is often dependent on the presence of prom...
journals.plos.org
September 15, 2025 at 7:04 PM
Very excited to share an excellent review from @teresa-urli.bsky.social, published one week before her PhD defense! We did a deep dive into the fascinating biology of the variant Polycomb complex, PRC1.6 (1/5) journals.plos.org/plosgenetics...
Reposted by The Lewis Lab
E. coli transcription factors regulate promoter activity by a universal, homeostatic mechanism | Science www.science.org/doi/10.1126/...
E. coli transcription factors regulate promoter activity by a universal, homeostatic mechanism
Transcription factors (TFs) may activate or repress gene expression through an interplay of different mechanisms, including RNA polymerase (RNAP) recruitment, exclusion, and initiation. However, depen...
www.science.org
September 11, 2025 at 7:19 PM
E. coli transcription factors regulate promoter activity by a universal, homeostatic mechanism | Science www.science.org/doi/10.1126/...
Reposted by The Lewis Lab
"Unmasked: transposable elements as drivers and targets in cancer"
by Ting Wang & colleagues
"This review synthesizes a growing body of work that positions TEs as both catalysts and antagonists of the tumor state."
Check it out!
authors.elsevier.com/sd/article/S...
by Ting Wang & colleagues
"This review synthesizes a growing body of work that positions TEs as both catalysts and antagonists of the tumor state."
Check it out!
authors.elsevier.com/sd/article/S...
September 11, 2025 at 1:53 PM
"Unmasked: transposable elements as drivers and targets in cancer"
by Ting Wang & colleagues
"This review synthesizes a growing body of work that positions TEs as both catalysts and antagonists of the tumor state."
Check it out!
authors.elsevier.com/sd/article/S...
by Ting Wang & colleagues
"This review synthesizes a growing body of work that positions TEs as both catalysts and antagonists of the tumor state."
Check it out!
authors.elsevier.com/sd/article/S...
Reposted by The Lewis Lab
Excited to share my postdoc work, out on bioRxiv today! Histones package DNA into nucleosomes to form the building blocks of chromatin, but how modular and programmable is this system? 1/9
September 11, 2025 at 7:55 PM
Excited to share my postdoc work, out on bioRxiv today! Histones package DNA into nucleosomes to form the building blocks of chromatin, but how modular and programmable is this system? 1/9
Reposted by The Lewis Lab
How can we understand the earliest events in evolution of eukaryotic immunity? @yao-li.bsky.social reports incredible molecular fossils of complete bacterial-like operons in eukaryotes that illuminate how animal immunity was first acquired from anti-phage defense
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
September 5, 2025 at 10:13 AM
How can we understand the earliest events in evolution of eukaryotic immunity? @yao-li.bsky.social reports incredible molecular fossils of complete bacterial-like operons in eukaryotes that illuminate how animal immunity was first acquired from anti-phage defense
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Reposted by The Lewis Lab
New preprint from my lab! We describe how transposable elements are activated in Parkinson’s disease, which is linked to an interferon response. We believe this study significantly advances our understanding of transposons and their role in human brains.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Activation of transposable elements is linked to a region- and cell-type-specific interferon response in Parkinson's disease
Parkinson's disease (PD) is a common age-related neurodegenerative disorder involving a neuroinflammatory response, the cause of which remains unclear. Transposable elements (TE) have been linked to i...
www.biorxiv.org
September 7, 2025 at 7:59 PM
New preprint from my lab! We describe how transposable elements are activated in Parkinson’s disease, which is linked to an interferon response. We believe this study significantly advances our understanding of transposons and their role in human brains.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Reposted by The Lewis Lab
#1 Centromeres are epigenetic loci defined by CENP-A, positioned in unmethylated DNA flanked by highly methylated regions. Our work, published in @natgenet.nature.com in collaboration with @naltemose.bsky.social investigates the role of DNAme at human centromeres www.nature.com/articles/s41...
DNA methylation influences human centromere positioning and function - Nature Genetics
Genome-wide and targeted perturbation of DNA methylation at centromeres affects CENP-A positioning and centromere structure, resulting in aneuploidy and reduced cell viability.
www.nature.com
September 4, 2025 at 1:10 PM
#1 Centromeres are epigenetic loci defined by CENP-A, positioned in unmethylated DNA flanked by highly methylated regions. Our work, published in @natgenet.nature.com in collaboration with @naltemose.bsky.social investigates the role of DNAme at human centromeres www.nature.com/articles/s41...
Reposted by The Lewis Lab
Delighted that our work on EZH2 dominant negativity in Weaver syndrome is now out in Genes & Development!
This exciting work on chromatinopathies 🧬 was in collab with @adrianbracken.bsky.social and spearheaded by Orla Deevy.
@ucddublin.bsky.social @ucd-sbbs.bsky.social
www.ucd.ie/newsandopini...
This exciting work on chromatinopathies 🧬 was in collab with @adrianbracken.bsky.social and spearheaded by Orla Deevy.
@ucddublin.bsky.social @ucd-sbbs.bsky.social
www.ucd.ie/newsandopini...
UCD co-lead breakthrough discovering genetic mechanism driving Weaver syndrome
www.ucd.ie
August 27, 2025 at 11:15 AM
Delighted that our work on EZH2 dominant negativity in Weaver syndrome is now out in Genes & Development!
This exciting work on chromatinopathies 🧬 was in collab with @adrianbracken.bsky.social and spearheaded by Orla Deevy.
@ucddublin.bsky.social @ucd-sbbs.bsky.social
www.ucd.ie/newsandopini...
This exciting work on chromatinopathies 🧬 was in collab with @adrianbracken.bsky.social and spearheaded by Orla Deevy.
@ucddublin.bsky.social @ucd-sbbs.bsky.social
www.ucd.ie/newsandopini...
Reposted by The Lewis Lab
New paper on the role of H3K4me3 at enhancers! We (led by Haoming Yu) used dCas9 epigenome editing to add H3K4me3 to intergenic enhancers. This was (1) sufficient to turn up transcription at open, active regions and (2) has no effect on target gene transcription. genesdev.cshlp.org/content/earl...
H3K4me3 amplifies transcription at intergenic active regulatory elements
A biweekly scientific journal publishing high-quality research in molecular biology and genetics, cancer biology, biochemistry, and related fields
genesdev.cshlp.org
August 20, 2025 at 1:29 AM
New paper on the role of H3K4me3 at enhancers! We (led by Haoming Yu) used dCas9 epigenome editing to add H3K4me3 to intergenic enhancers. This was (1) sufficient to turn up transcription at open, active regions and (2) has no effect on target gene transcription. genesdev.cshlp.org/content/earl...
Reposted by The Lewis Lab
I am very excited to share the newest paper of the lab, a huge amount of work led by our talented PhD student Maxime Galloy, in close collaboration with Andréanne Blondeau, our dedicated research assistant for 10 years! 🙌
www.cell.com/molecular-ce...
www.cell.com/molecular-ce...
Ubiquitination of the histone variant mH2A1.2 prevents toxic RAD18 accumulation at a subset of genomic loci upon replication stress
Using biochemical assays and a mutant disrupting RNF168-dependent ubiquitination of
the histone variant macroH2A1.2, Galloy et al. identified an unexpected role for histone
mH2A1.2 ubiquitination in p...
www.cell.com
August 13, 2025 at 3:20 PM
I am very excited to share the newest paper of the lab, a huge amount of work led by our talented PhD student Maxime Galloy, in close collaboration with Andréanne Blondeau, our dedicated research assistant for 10 years! 🙌
www.cell.com/molecular-ce...
www.cell.com/molecular-ce...
Reposted by The Lewis Lab
I am thrilled to share with you my first co-corresponding author Nature paper with Jos Jonkers. This project was led by the extraordinary @sarahmoser.bsky.social . Congratulations, and thank you to all the authors, @nkinl.bsky.social , and @oncodeinstitute.bsky.social for their support.
August 13, 2025 at 3:57 PM
I am thrilled to share with you my first co-corresponding author Nature paper with Jos Jonkers. This project was led by the extraordinary @sarahmoser.bsky.social . Congratulations, and thank you to all the authors, @nkinl.bsky.social , and @oncodeinstitute.bsky.social for their support.
Reposted by The Lewis Lab
The summer has been busy! Along with the move and a PhD defense, we have updated two preprints:
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
The chemotherapy-induced senescence-associated secretome promotes cell detachment and metastatic dissemination through metabolic reprogramming
Cellular senescence, characterized by a stable cell cycle arrest, is a well-documented consequence of several widely used chemotherapeutics that has context-dependent roles in cancer. Although senesce...
www.biorxiv.org
August 14, 2025 at 12:03 PM
The summer has been busy! Along with the move and a PhD defense, we have updated two preprints:
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Reposted by The Lewis Lab
What better way to launch our new account with the publication of @jmstein.bsky.social latest paper from the lab! 🧪 Check out the 🧵 below to learn more about tkPAINT and how we use it to image proteins, DNA, and RNA in the nucleus using DNA-PAINT.
(1/n) DNA-PAINT imaging inside the nucleus at single antibody resolution using TIRF? Ultrathin sectioning makes it happen!
Grateful to share my postdoctoral work introducing “tomographic & kinetically-enhanced DNA-PAINT” or in brief: tkPAINT. Out in @pnas.org!
doi.org/10.1073/pnas...
👇🧵
Grateful to share my postdoctoral work introducing “tomographic & kinetically-enhanced DNA-PAINT” or in brief: tkPAINT. Out in @pnas.org!
doi.org/10.1073/pnas...
👇🧵
August 13, 2025 at 6:16 PM
What better way to launch our new account with the publication of @jmstein.bsky.social latest paper from the lab! 🧪 Check out the 🧵 below to learn more about tkPAINT and how we use it to image proteins, DNA, and RNA in the nucleus using DNA-PAINT.
Reposted by The Lewis Lab
Epigenetics Update - The molecular basis of lamin-specific chromatin interactions go.nature.com/3GRXydB
Chiara Lanzuolo (INGM) and Ohad Medalia (University of Zurich) reporting in NSMB
#Epigenetics #Chromatin #Lamin
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Gain deeper insights into gene regulation; epigenometech.com
Chiara Lanzuolo (INGM) and Ohad Medalia (University of Zurich) reporting in NSMB
#Epigenetics #Chromatin #Lamin
---
Gain deeper insights into gene regulation; epigenometech.com
The molecular basis of lamin-specific chromatin interactions - Nature Structural & Molecular Biology
Wang, Kronenberg-Tenga, Rosti and colleagues use several structural approaches to analyze the distribution of nucleosomes at the lamin–chromatin interface, test the impact of lamins on nucleosome dens...
go.nature.com
August 4, 2025 at 1:11 PM
Epigenetics Update - The molecular basis of lamin-specific chromatin interactions go.nature.com/3GRXydB
Chiara Lanzuolo (INGM) and Ohad Medalia (University of Zurich) reporting in NSMB
#Epigenetics #Chromatin #Lamin
---
Gain deeper insights into gene regulation; epigenometech.com
Chiara Lanzuolo (INGM) and Ohad Medalia (University of Zurich) reporting in NSMB
#Epigenetics #Chromatin #Lamin
---
Gain deeper insights into gene regulation; epigenometech.com
Reposted by The Lewis Lab
Excited to share our latest preprint. www.biorxiv.org/content/10.1.... Lead by Lukas, we investigated multiple ways of assessing a TF's sensitivity to chromatin based on genome-wide binding profiles. The developed methods allowed us to quantify chromatin sensitivity across tested TFs.
A novel deep learning-based framework reveals a continuum of chromatin sensitivities across transcription factors
The genome-wide binding of many transcription factors (TFs) depends not only on the presence of their recognition motifs, but also on the surrounding chromatin context. This raises the question of how...
www.biorxiv.org
August 12, 2025 at 8:32 AM
Excited to share our latest preprint. www.biorxiv.org/content/10.1.... Lead by Lukas, we investigated multiple ways of assessing a TF's sensitivity to chromatin based on genome-wide binding profiles. The developed methods allowed us to quantify chromatin sensitivity across tested TFs.