#SETD2
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
December 12, 2024 at 7:16 PM
Ever wondered what else SETD2 does beyond transcription? 🧬
Check out our new ‪@natcellbio.nature.com‬ study.
Awesome work from Abid Khan in the lab SETD2 moonlights during mitosis to keep the genome safe from chaos.showing how SETD2 moonlights to safeguard the genome during cell division.
August 11, 2025 at 12:26 PM
Pol2 stimulates
SETD2 methylation
Of histone H3

#ChromatinHaiku #H3K36
www.science.org/doi/10.1126/...
December 13, 2024 at 3:39 PM
December 13, 2024 at 2:23 AM
Happy to share latest work from the lab. Led by talented first author @awmartinelli.bsky.social. Mapping the genetic landscape of iron metabolism uncovers the SETD2 methyltransferase as a modulator of iron flux | Science Advances www.science.org/doi/10.1126/... Congratulations to all the team.
Mapping the genetic landscape of iron metabolism uncovers the SETD2 methyltransferase as a modulator of iron flux
Genetic screens using endogenous reporters map key modulators of cellular iron, including the transcriptional regulator SETD2.
www.science.org
September 18, 2025 at 7:02 PM
Our story on the mechanism of co-transcriptional histone mark deposition is now officially out: www.science.org/doi/10.1126/...
Structural basis of H3K36 trimethylation by SETD2 during chromatin transcription
During transcription, RNA polymerase II traverses through chromatin, and posttranslational modifications including histone methylations mark regions of active transcription. Histone protein H3 lysine ...
www.science.org
January 30, 2025 at 10:16 PM
💫NEW: @brianstrahl.bsky.social & co report a non-catalytic function of the methyltransferase SETD2 in regulating nuclear morphology and genome integrity.
👉https://rdcu.be/eBW3D
bit.ly/3Vff6DO
A SETD2–CDK1–lamin axis maintains nuclear morphology and genome stability - Nature Cell Biology
Khan et al. report a non-catalytic function of the methyltransferase SETD2 in regulating nuclear morphology and genome integrity. The SETD2 amino terminus functions as a scaffold helping CDK1 associat...
bit.ly
August 22, 2025 at 5:28 PM
Preprint Alert! Check out our take on the molecular basis for co-transcriptional H3K36me3 deposition by SETD2. www.biorxiv.org/content/10.1...
Molecular mechanism of co-transcriptional H3K36 methylation by SETD2
Tri-methylation of histone H3 at residue lysine-36 (H3K36me3) is a hallmark of actively and recently transcribed genes and contributes to cellular memory and identity. The deposition of H3K36me3 occur...
www.biorxiv.org
December 14, 2024 at 1:50 PM
With 8 composite cryo-EM maps (totaling 47 EMDB entries) and several biochemical assays, we demonstrate the mechanistic basis for the positioning of H3K36me3 within actively transcribed regions. Surprisingly, SETD2 must be relieved of auto inhibition by the transcription machinery!
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
December 12, 2024 at 7:54 PM
In our SETD2 paper, we visualize a novel nucleosome transfer intermediate during txn. It is the earliest intermediate visualized yet. In the intermediate, the histone chaperone FACT coordinates histone binding with a previously uncharacterized RTF1 helix. All details in the paper: tinyurl.com/setd2
December 12, 2024 at 7:30 PM
This Friday @uam-ibmib.bsky.social seminar: Magda Kopczyńska @mgkopczynska.bsky.social (@stoplab.bsky.social) on #SETD2 methyltransferase activity in gene definition and transcription regulation. Don't miss it! #epigenetics #transcriptionTermination #chromatin
December 19, 2025 at 6:42 AM
🚨 New preprint from our labs (STOP lab @stoplab.bsky.social & Nojima lab @pol2rna.bsky.social @pyrolyn.bsky.social)! We've been digging into how chromatin remodeler SETD2 controls the start and end of transcription 👇 www.biorxiv.org/cgi/content/... (1/5)
July 16, 2025 at 9:38 AM
SETD2 H3K36 methyltransferase
Pancreas development
e11.5/13.5/15.5

PDX+ pancreatic progenitor Setd2 KO🐭
👉⏫Exocrine cell proliferation + perturbed tip-to-acinar trajectory
👉⏬α/β Islets ⏫blood glucose

NKX2.2➡️endocrine specification

#CellRep 2024
www.sciencedirect.com/science/arti...
July 1, 2025 at 11:15 AM
🧪Wonderful study and visualization from @lucas.farnunglab.com and @jonmarkert.bsky.social, uncovering how SETD2 - an important but challenging cancer drug target - interacts with chromatin to catalyze H3K36me3. Congratulations to all involved!
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
December 13, 2024 at 2:44 PM
H3K36me3 modification by SETD2 is essential for Col11a2 and Sema3e transcription to maintain dentinogenesis in mice.

Read this Research Article by Jiaxin Niu and Guohua Yuan's group:
journals.biologists.com/dev/article/...
July 27, 2025 at 12:55 PM
Are you interested in hearing this SETD2 story in more detail? I’ll be presenting it at @fnucleosome.bsky.social this week! Please see the poster for more details
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
March 10, 2025 at 2:20 PM
For more details, dive into our manuscript: tinyurl.com/setd2
Stay tuned for more insights into chromatin biology and transcription dynamics. Feedback & questions welcome! #Transcription #Epigenetics
Structural basis of H3K36 trimethylation by SETD2 during chromatin transcription
During transcription, RNA polymerase II traverses through chromatin, and post-translational modifications including histone methylations mark regions of active transcription. Histone protein H3 lysine...
tinyurl.com
December 12, 2024 at 7:20 PM
Very surprisingly, upstream nucleosomes appear to be SETD2's preferred substrates, highlighting a coordinated interplay between transcription elongation and histone modification where SETD2 can methylate both the proximal and distal H3 of the upstream nucleosome, establishing the H3K36me3 landscape.
December 12, 2024 at 7:20 PM
UNC scientists uncovered a hidden role for the tumor suppressor gene SETD2. Now, thanks to the work of Dr. @brianstrahl.bsky.social and Dr. Abid Khan, we know SETD2 also plays a key structural role in maintaining nuclear integrity during cell division! go.unc.edu/SETD2 @brianstrahl.bsky.social
UNC Scientists Uncover Hidden Role of Tumor Suppressor Gene in Protecting the Genome | Newsroom
In a surprising twist, UNC scientists discovered that SETD2, a tumor suppressor best known for modifying DNA-packaging proteins, also preserves nuclear structure during cell division—a hidden role tha...
go.unc.edu
August 14, 2025 at 7:27 PM
SETD2 binds unwrapped nucleosomes via the catalytic SET domain & relies on interactions with SPT6. The SPT6 death-like domain (DLD) anchors SETD2, ensuring precise H3K36me3 deposition and relieves the auto-inhibitory domain of SETD2 to activate its methyltransferase activity.
December 12, 2024 at 7:20 PM
New week, insights! ✨ The team led by Kinga Kamieniarz-Gdula (@stoplab.bsky.social) reveals in EMBO Reports how SETD2 acts as a genetic "traffic controller." A vital step in understanding cancer biology!

Congrats to @michal-gdula.bsky.social, @agatakstepien.bsky.social, @mgkopczynska.bsky.social! 👏
SETD2 methyltransferase activity promotes correct transcription initiation and termination - EMBO Reports
SETD2 is a methyltransferase responsible for depositing histone H3 lysine 36 trimethylation (H3K36me3). Loss of its enzymatic activity occurs in some cancers, including renal cell carcinoma. SETD2 mut...
link.springer.com
April 27, 2026 at 5:32 PM
SETD2 aids gene definition by acting on both its beginning and end - yet in a gene specific way.
Proud of this new work from the lab! @uam-ibmib.bsky.social @emboreports.org #chromatin #RNAbiology
Our paper (@stoplab.bsky.social), in collaboration with the Nojima lab (@pol2rna.bsky.social @chiheron.bsky.social), on the role of chromatin modifier SETD2 at both ends of the transcriptional cycle, is now published in @emboreports.org 🪅 (1/5)
link.springer.com/article/10.1...
April 21, 2026 at 11:42 AM
Our paper (@stoplab.bsky.social), in collaboration with the Nojima lab (@pol2rna.bsky.social @chiheron.bsky.social), on the role of chromatin modifier SETD2 at both ends of the transcriptional cycle, is now published in @emboreports.org 🪅 (1/5)
link.springer.com/article/10.1...
April 17, 2026 at 5:23 PM
Epigenetics Update - A SETD2–CDK1–lamin axis maintains nuclear morphology and genome stability go.nature.com/4mgxhVM

Brian D. Strahl (U at Chapel Hill) reporting in Nat Cell Biol

#Epigenetics #SETD2 #H3K36me3
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Perfect for cancer, immunology, and aging research; epigenometech.com
A SETD2–CDK1–lamin axis maintains nuclear morphology and genome stability - Nature Cell Biology
Khan et al. report a non-catalytic function of the methyltransferase SETD2 in regulating nuclear morphology and genome integrity. The SETD2 amino terminus functions as a scaffold helping CDK1 associat...
go.nature.com
August 12, 2025 at 7:58 AM