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PRMT5 activity sustains histone production to maintain genome integrity

Why can’t cells live without PRMT5? Our new transformative work inspired and led by @jacobroth13.bsky.social (who defends his thesis tomorrow!) shows that this arginine methyltransferase is critical for histone production and genome stability. Full story: www.biorxiv.org/content/10.1... 1/5

biorxiv.org

Histone proteins package DNA into nucleosomes, forming chromatin and thereby safeguarding genome integrity. Proper histone expression is essential for cell proliferation and chromatin organization, ye...

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PRMT5 activity sustains histone production to maintain genome integrity

This feedback loop explains why PRMT5 is cell-essential: by coordinating histone supply, PRMT5 ensures proper chromatin assembly, genome integrity & cell proliferation. No PRMT5 = no histones = stalled growth. @JacobRoth13. Check it out: doi.org/10.1101/2025.07.03.663002 5/5

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Mechanistically, soluble histone H4 accumulates at histone locus bodies upon PRMT5 inhibition, and H4 R3 mutants localize more robustly than WT—supporting methylation-driven feedback at histone loci. 4/5

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Inhibiting or knocking down PRMT5 triggers rapid histone mRNA depletion, histone protein loss & replication-associated nuclear abnormalities (micronuclei, γH2AX foci), directly linking arginine methylation to genome stability. 3/5

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Using time-resolved nascent transcription profiling, quantitative proteomics & imaging, we show that PRMT5 is required to sustain histone mRNA transcription & histone protein synthesis during S-phase—when demand for new histones peaks. 2/5

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PRMT5 activity sustains histone production to maintain genome integrity

biorxiv.org

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Reposted by David Shechter

Christopher Webb @cwebbonline.com · 12/06/2025

Powerful statement by Sen. Alex Padilla. Please notice that anytime senators or representatives try to conduct oversight, they’re blocked. In this case, a sitting US senator was tackled to the ground and handcuffed—for asking a question. Where the hell has Chuck Schumer been on this?

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David Shechter @dshechter.bsky.social · 12/05/2025

For all my NYC Chromatin / Epigenetics / Gene Expression colleagues - the registration and abstract deadline for our Summer '25 symposium is this Friday. Attendance is free (lunch and coffee breaks provided), but we need you to sign up! See here: mailchi.mp/cbee4a4e6267...

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Yael David @yaeldavidmsk.bsky.social · 05/05/2025

Excited for this summer’s NYC Chromatin Club! Grad students & postdocs: submit your abstracts for a chance to present a poster or talk. Come connect w/ fellow epigenetic New Yorkers! #NYCChromatinClub @dshechter.bsky.social @vivrisca.bsky.social @epicypher.bsky.social @kjarmache.bsky.social

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bioRxivpreprint @biorxivpreprint.bsky.social · 10/04/2025

TTLL4 glutamyltransferase is a therapeutic target for NPM1-mutated acute myeloid leukemia www.biorxiv.org/content/10.1101/202…

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Reposted by David Shechter

bioRxiv Cancer Bio @biorxiv-cancer.bsky.social · 10/04/2025

TTLL4 glutamyltransferase is a therapeutic target for NPM1-mutated acute myeloid leukemia www.biorxiv.org/content/10.1101/202…

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That foundation of basic science, funded by the NIH and DoD/CDMRP, led us here: to a druggable AML vulnerability. Basic science matters. So does federal funding. /end

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This story began with our curiosity-driven work in Xenopus frogs and proteins—studying glutamate-glutamylation in basic chromatin biology of histone chaperone function. bit.ly/4j7uEnB and and go.nature.com/42GgDXW and bit.ly/3XVCrMJ /7

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Redirecting

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TTLL4 is a post-translational regulator of leukemia maintenance. It’s druggable. It’s specific. And it’s a promising new angle in a challenging AML subtype. This is exactly the kind of science made possible by federal funding. /6

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We didn’t stop there: Through biochemical and virtual screening, we identified TTLL4 inhibitors. One compound, EN7, selectively impairs NPM1c AML cells—while sparing wildtype cells. /5

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In a Npm1c;NrasG12D/+ mouse model, Ttll4 deletion reduced leukemia burden and significantly prolonged survival. /4

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TTLL4 adds a glutamyl group to NPM1 at E126. Without it, NPM1c shifts back to the nucleus—disrupting its ability to sustain leukemia. Loss of TTLL4 phenocopies NPM1c degradation: Lower proliferation, more myeloid differentiation, and broad gene expression changes. /3

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Many years of effort by @alexkschurer.bsky.social and @humaira2204.bsky.social , following initial work by Maxim Maron, lead us to this discovery. /2

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TTLL4 glutamyltransferase is a therapeutic target for NPM1-mutated acute myeloid leukemia

We discovered a new AML vulnerability: TTLL4 glutamylates NPM1c and helps leukemia cells thrive. Knock it down and cells differentiate and survival improves. Collab between our lab and @Gritsman_lab—funded by NIH and DoD/CDMRP. Preprint: bit.ly/42oZl09 /1

bit.ly

NPM1-mutated acute myeloid leukemia (AML) is defined by aberrant cytoplasmic localization of the mutant NPM1c protein, and therapeutic strategies targeting this specific disease remain limited. Here, ...

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Mike the Mad Biologist and Trump's Press Corps Approver @mikethemadbiol.bsky.social · 09/04/2025

Every post Trump makes about tariffs sounds like a late night used car commercial. Waiting for the post that starts with “I just spoke to my manager and I think we can get you down to ten percent…”

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John Wallingford @jbwallingford.bsky.social · 02/04/2025

Director of the Nat'l Institute of Child Health and Human Development (NICHD) was summarily dismissed yesterday. So here's your reminder that birth defects kill twice as many American kids as cancer. But there is no St. Jude's for birth defects. Only the NICHD. www.nature.com/articles/d41...

nature.com

‘One of the darkest days’: NIH purges agency leadership amid mass layoffs

In shock move, four institute directors at the US biomedical agency are removed from their posts.

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Reposted by David Shechter

Jeremy Berg @jeremymberg.bsky.social · 29/03/2025

Analysis of Terminated NIH Grants with Word Clouds First, using the titles of grants not to Columbia... Gender and DEI predominate

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Reposted by David Shechter

Mark Peifer (He, him) @peiferlabunc.bsky.social · 26/03/2025

14 pages of terminated NIH grants--everyone should read through the list. The sweep is VERY broad, including "The Impact of the Herpes Zoster Vaccine on Herpes Zoster Ophthalmicus" & "Mitochondrial-based Determinants of Sex Differences in Acute Kidney Injury"🧪 1/n taggs.hhs.gov/Content/Data...

taggs.hhs.gov

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Yell In a War @jelenawoehr.bsky.social · 24/03/2025

Jeffrey Goldberg thinking he was being pranked and then realizing he was actually just in the war plans group chat is such a good microcosm of how it feels to be alive right now, everything seems fake until you realize it’s actually real and incredibly stupid

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David Atkins @davidoatkins.bsky.social · 15/03/2025

Trump and Musk are basically trying to deskill America: 1) kill all white-collar jobs and replace them with AI 2) kill universities 3) use tariffs to turn the U.S. into an economic island manufacturing, oil and ag hub 4) empty the cities 5) push men into manual labor & women back into the kitchen

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Derek Lowe @dereklowe.bsky.social · 05/03/2025

Another “Continuing Crisis” post, this one covering some larger principles and explaining why I’m doing these in general:

science.org

The Continuing Crisis, Part VII: An Overview

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Jeremy Berg @jeremymberg.bsky.social · 02/03/2025

I am not going to call this a Bluetorial, because I do not want to sully that term (which, at least I, find joyful). Let’s call it a Orwellial.

a cartoon of homer simpson holding a card

ALT: a cartoon of homer simpson holding a card

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Jeremy Berg @jeremymberg.bsky.social · 22/02/2025

Bluetorial: The path to a new pain medication with little potential for addiction Perhaps a good story to share with folks who want to learn about how biomedical research works and where advances come from.

a cartoon says hey everybody an old man 's talking while bart simpson looks on

ALT: a cartoon says hey everybody an old man 's talking while bart simpson looks on

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Jeremy Berg @jeremymberg.bsky.social · 21/02/2025

I have heard from several sources (although details are vague) it appears that NIH is back to blocking NoA release while awaiting development of plans for dealing language, perhaps pertaining to DEI issues, in these awards. If this is occurring, it seems like a clear violation of the TRO. 1/n

patrick star and spongebob squarepants from spongebob squarepants are standing next to each other in a dark room .

ALT: patrick star and spongebob squarepants from spongebob squarepants are standing next to each other in a dark room .

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Derek Lowe @dereklowe.bsky.social · 20/02/2025

Want a moral? Lawlessness is not just an exciting chance to make big money. Autocrats won’t always be on your side. You are better off under the boring, confining rule of law, because once it’s been demolished you are not in control of anything. Perhaps no one is. Especially not you. (8/8)

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Jeremy Berg @jeremymberg.bsky.social · 21/02/2025

The only conclusion that I can draw is that their answer to this question is: Yeah, what about it? They just don’t care or think the private sector can do this, without realizing the complementary interests and skills of the public and private sectors. 3/n

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Derek Lowe @dereklowe.bsky.social · 19/02/2025

This is absolutely pathetic. Saying nothing was bad enough, but this?

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Rick Huganir @rhuganir.bsky.social · 15/02/2025

I have been talking to the media, Time, Fortune, NBC, etc., to explain how the onslaught on science and NIH will impact the health of all Americans. Everyone knows someone who has cancer, heart disease, or depression. Spread the word about how cutting science impacts all. time.com/7216299/nih-...

time.com

Experts Call NIH Budget Cuts an 'Apocalypse' for Science

The reductions target indirect costs that cover administrative and equipment costs.

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Jeremy Berg @jeremymberg.bsky.social · 15/02/2025

They are absolutely cutting science! Folks in the NIH intramural program are gone. Folks in extramural programs. These include PhD and MD scientists who help make NIH function as a granting agency. They are depict this as cutting easily replaceable bureaucrat. There aren't many of those at NIH.