The Lewis Lab
@peterlewislab.bsky.social
Chromatin biochemistry and genomics in development and cancer. UW-Madison School of Medicine and Public Health
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 paper from my lab out in NAR. We found that young L1 elements are controlled by SETDB1 and H3K9me3 in human neural progenitor cells via a mechanism independent of HUSH and TRIM28/KZNFs.
academic.oup.com/nar/article/...
academic.oup.com/nar/article/...
Loss of SETDB1-mediated H3K9me3 in human neural progenitor cells leads to transcriptional activation of L1 retrotransposons
Abstract. Heterochromatin is characterized by an inaccessibility to the transcriptional machinery and is associated with the histone mark H3K9me3. However,
academic.oup.com
February 5, 2026 at 3:17 PM
New paper from my lab out in NAR. We found that young L1 elements are controlled by SETDB1 and H3K9me3 in human neural progenitor cells via a mechanism independent of HUSH and TRIM28/KZNFs.
academic.oup.com/nar/article/...
academic.oup.com/nar/article/...
Reposted by The Lewis Lab
H3K79me2/3 is sufficient to antagonise PRC1 www.nature.com/articles/s41...
DOT1L provides transcriptional memory through PRC1.1 antagonism - Nature Cell Biology
Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibit...
www.nature.com
February 3, 2026 at 10:30 PM
H3K79me2/3 is sufficient to antagonise PRC1 www.nature.com/articles/s41...
Reposted by The Lewis Lab
Now final version out: Our manuscript connecting histone modifications with metabolism: How H4K16 acylations regulate inter +intranucleosomal interactions and confer resilience to metabolic challenges in vivo. Thanks to the team+ @sandrani.bsky.social
Enjoy 👇👇 www.cell.com/molecular-ce...
Enjoy 👇👇 www.cell.com/molecular-ce...
H4K16 acylations destabilize chromatin architecture and facilitate transcriptional response during metabolic perturbations
Nitsch et al. show that short-chain acylations of histone H4K16, acetylation (C2),
propionylation (C3), and butyrylation (C4) modulate chromatin structure in vitro.
These effects can translate in vivo...
www.cell.com
January 9, 2026 at 12:22 PM
Now final version out: Our manuscript connecting histone modifications with metabolism: How H4K16 acylations regulate inter +intranucleosomal interactions and confer resilience to metabolic challenges in vivo. Thanks to the team+ @sandrani.bsky.social
Enjoy 👇👇 www.cell.com/molecular-ce...
Enjoy 👇👇 www.cell.com/molecular-ce...
Reposted by The Lewis Lab
Happy to share with you our work on how the interferon response impacts embryonic development 🦠Mammalian embryos contain endogenous dsRNAs that resemble viruses and can be misrecognised by the dsRNA sensor MDA5.
Thanks to all collaborators, we could not have done it without you 🤩
rdcu.be/eWMfA
Thanks to all collaborators, we could not have done it without you 🤩
rdcu.be/eWMfA
Double stranded RNA sensing is silenced during early embryonic development
Nature Communications - The type I interferon response is suppressed during early development, making embryos susceptible to pathogens. Here, the authors show that this suppression contributes to...
rdcu.be
January 7, 2026 at 3:28 PM
Happy to share with you our work on how the interferon response impacts embryonic development 🦠Mammalian embryos contain endogenous dsRNAs that resemble viruses and can be misrecognised by the dsRNA sensor MDA5.
Thanks to all collaborators, we could not have done it without you 🤩
rdcu.be/eWMfA
Thanks to all collaborators, we could not have done it without you 🤩
rdcu.be/eWMfA
Reposted by The Lewis Lab
Stress controls epigenetic inheritance!
A histone ubiquitylation-based regulatory hub links stress/environmental signaling to heterochromatin self-propagation and epigenetic inheritance-reshaping how we think about development, drug resistance, and cancer
👉 nature.com/articles/s41586-025-09899-8
A histone ubiquitylation-based regulatory hub links stress/environmental signaling to heterochromatin self-propagation and epigenetic inheritance-reshaping how we think about development, drug resistance, and cancer
👉 nature.com/articles/s41586-025-09899-8
January 7, 2026 at 4:46 PM
Stress controls epigenetic inheritance!
A histone ubiquitylation-based regulatory hub links stress/environmental signaling to heterochromatin self-propagation and epigenetic inheritance-reshaping how we think about development, drug resistance, and cancer
👉 nature.com/articles/s41586-025-09899-8
A histone ubiquitylation-based regulatory hub links stress/environmental signaling to heterochromatin self-propagation and epigenetic inheritance-reshaping how we think about development, drug resistance, and cancer
👉 nature.com/articles/s41586-025-09899-8
Nice structural and biochemical dissection of how ATRX engages nucleosomes and couples ATP hydrolysis to productive sliding via a distinctive mechanism. www.biorxiv.org/content/10.6...
January 7, 2026 at 1:09 AM
Nice structural and biochemical dissection of how ATRX engages nucleosomes and couples ATP hydrolysis to productive sliding via a distinctive mechanism. www.biorxiv.org/content/10.6...
Reposted by The Lewis Lab
Need a bit of escapism? Not exactly Lord of the Rings, but in similar vein:
doi.org/10.1038/s443...
doi.org/10.1038/s443...
Epimutations: raw material for evolution? - The EMBO Journal
Epigenetics is fundamental to cell differentiation as it enables cells with identical genomes to adopt distinct fates. Some epigenetic information can also be transmitted between generations, in a pro...
link.springer.com
January 6, 2026 at 6:33 PM
Need a bit of escapism? Not exactly Lord of the Rings, but in similar vein:
doi.org/10.1038/s443...
doi.org/10.1038/s443...
Reposted by The Lewis Lab
Now online in Cancer Discovery @aacrjournals.bsky.social: LINE-1 Locus Transcription Nucleates Oncogenic Chromatin Architecture - by Michael Lee, Yuannyu Zhang, Jian Xu, and colleagues doi.org/10.1158/2159... @stjuderesearch.bsky.social
January 6, 2026 at 7:11 PM
Now online in Cancer Discovery @aacrjournals.bsky.social: LINE-1 Locus Transcription Nucleates Oncogenic Chromatin Architecture - by Michael Lee, Yuannyu Zhang, Jian Xu, and colleagues doi.org/10.1158/2159... @stjuderesearch.bsky.social
What in the name of S-adenosylmethionine is this.... Somewhere a DNMT is drafting a strongly worded letter to this worksheet.
December 15, 2025 at 11:47 PM
What in the name of S-adenosylmethionine is this.... Somewhere a DNMT is drafting a strongly worded letter to this worksheet.
Reevaluation of whether histones are asymmetrically segregated during asymmetric divisions of stem cells in Drosophila | PNAS www.pnas.org/doi/10.1073/...
Reevaluation of whether histones are asymmetrically segregated during asymmetric divisions of stem cells in Drosophila | PNAS
Recent work suggests that asymmetric segregation of preexisting and newly synthesized
canonical histone 3.1 (H3.1), but not variant histone 3.3A (H...
www.pnas.org
December 14, 2025 at 5:08 PM
Reevaluation of whether histones are asymmetrically segregated during asymmetric divisions of stem cells in Drosophila | PNAS www.pnas.org/doi/10.1073/...
Reposted by The Lewis Lab
@pravrutharaman.bsky.social got super intrigued about EZHIP/CATACOMB, previously identified as a histone H3K27M mimic of PRC2. You can read about her efforts here: www.biorxiv.org/content/10.6... We hope these analyses will help spur more analyses in this very cool gene! 1/
Dynamic evolution of EZHIP, an inhibitor of the Polycomb Repressive Complex 2 in mammals
The Polycomb Repressive Complex 2 (PRC2) is an ancient, conserved chromatin-interacting complex that controls gene expression, facilitating differentiation and cellular identity during development. It...
www.biorxiv.org
December 13, 2025 at 10:08 PM
@pravrutharaman.bsky.social got super intrigued about EZHIP/CATACOMB, previously identified as a histone H3K27M mimic of PRC2. You can read about her efforts here: www.biorxiv.org/content/10.6... We hope these analyses will help spur more analyses in this very cool gene! 1/
Reposted by The Lewis Lab
An early Christmas present for those interested in chromatin and transcription! Fantastic work from @au-ho-yu.bsky.social and @aleksszczurek.bsky.social . Thanks to Inge and Michiel for their help. Please repost!
www.biorxiv.org/content/10.6...
www.biorxiv.org/content/10.6...
SET1/MLL complexes control transcription independently of H3K4me3
Histone H3 lysine 4 trimethylation (H3K4me3) at gene promoters is thought to play a central role in gene transcription. H3K4 methylation is deposited by the SET1 (A/B) and MLL (1-4) multi-protein comp...
www.biorxiv.org
December 11, 2025 at 6:09 AM
An early Christmas present for those interested in chromatin and transcription! Fantastic work from @au-ho-yu.bsky.social and @aleksszczurek.bsky.social . Thanks to Inge and Michiel for their help. Please repost!
www.biorxiv.org/content/10.6...
www.biorxiv.org/content/10.6...
Reposted by The Lewis Lab
Our Science paper is out!
Huge congratulations to @huabin-zhou.bsky.social, Mike Rosen, and the brilliant @janhuemar.bsky.social @juliamaristany.bsky.social and @kieran-russell.bsky.social from our group
News: bit.ly/4avnkAr and bit.ly/3XBGVHS
Great perspective by @vram142.bsky.social +K Zhang
Huge congratulations to @huabin-zhou.bsky.social, Mike Rosen, and the brilliant @janhuemar.bsky.social @juliamaristany.bsky.social and @kieran-russell.bsky.social from our group
News: bit.ly/4avnkAr and bit.ly/3XBGVHS
Great perspective by @vram142.bsky.social +K Zhang
December 5, 2025 at 9:47 AM
Our Science paper is out!
Huge congratulations to @huabin-zhou.bsky.social, Mike Rosen, and the brilliant @janhuemar.bsky.social @juliamaristany.bsky.social and @kieran-russell.bsky.social from our group
News: bit.ly/4avnkAr and bit.ly/3XBGVHS
Great perspective by @vram142.bsky.social +K Zhang
Huge congratulations to @huabin-zhou.bsky.social, Mike Rosen, and the brilliant @janhuemar.bsky.social @juliamaristany.bsky.social and @kieran-russell.bsky.social from our group
News: bit.ly/4avnkAr and bit.ly/3XBGVHS
Great perspective by @vram142.bsky.social +K Zhang
Reposted by The Lewis Lab
Very proud to have our latest work now online in
@natsmb.nature.com. A wonderful team effort across the centromere community, across @jansenlab.bsky.social @naltemose.bsky.social @dfachinetti.bsky.social and Giunta labs. Happy reading! 1/4
www.nature.com/articles/s41...
@natsmb.nature.com. A wonderful team effort across the centromere community, across @jansenlab.bsky.social @naltemose.bsky.social @dfachinetti.bsky.social and Giunta labs. Happy reading! 1/4
www.nature.com/articles/s41...
Heterochromatin boundaries maintain centromere position, size and number - Nature Structural & Molecular Biology
Carty et al. identify the H3K9 methyltransferases that restrict the size and position of the centromere protein A chromatin domain, maintaining functional centromeres.
www.nature.com
November 27, 2025 at 9:58 PM
Very proud to have our latest work now online in
@natsmb.nature.com. A wonderful team effort across the centromere community, across @jansenlab.bsky.social @naltemose.bsky.social @dfachinetti.bsky.social and Giunta labs. Happy reading! 1/4
www.nature.com/articles/s41...
@natsmb.nature.com. A wonderful team effort across the centromere community, across @jansenlab.bsky.social @naltemose.bsky.social @dfachinetti.bsky.social and Giunta labs. Happy reading! 1/4
www.nature.com/articles/s41...
Reposted by The Lewis Lab
How to keep in step when your (protein) partner speeds up…
Here we investigated the adaptive remodeling of a protein-protein interaction surface essential for telomere protection.
Congrats to whole team!
www.science.org/doi/10.1126/...
Here we investigated the adaptive remodeling of a protein-protein interaction surface essential for telomere protection.
Congrats to whole team!
www.science.org/doi/10.1126/...
Rapid compensatory evolution within a multiprotein complex preserves telomere integrity
Intragenomic conflict with selfish genetic elements spurs adaptive changes in subunits of essential multiprotein complexes. Whether and how these adaptive changes disrupt interactions within such comp...
www.science.org
November 28, 2025 at 5:22 PM
How to keep in step when your (protein) partner speeds up…
Here we investigated the adaptive remodeling of a protein-protein interaction surface essential for telomere protection.
Congrats to whole team!
www.science.org/doi/10.1126/...
Here we investigated the adaptive remodeling of a protein-protein interaction surface essential for telomere protection.
Congrats to whole team!
www.science.org/doi/10.1126/...
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...