Our new study shows a CHD-family remodeler can nucleate and spread H3K9 methylation de novo, inverting the canonical hierarchy between writers and remodelers. www.biorxiv.org/content/10.6...

Nucleosome remodeling by a CHD enzyme promotes H3K9 methylation establishment and spreading via remodeler-writer feedback

In Schizosaccharomyces pombe , the conserved CHD remodeler Mit1 function within the SHREC remodeler-deacetylase complex (a homolog of the metazoan Mi-2/NuRD complex), which is essential for H3K9 methy...

biorxiv.org

New PARP1 preprintfrom the lab, by Alex Fiorenza and our amazing undergrad Mahika Anand. PARP1 functions in DNA repair, but what about its second gig as a chromatin architectural protein? How does it stay enzymatically quiet? Read all about it here. www.biorxiv.org/content/10.6...

PARP1 Exhibits an Enzymatically Inactive Chromatin Binding Mode

Poly (ADP-ribose) Polymerase 1 (PARP1) is an abundant nuclear enzyme that dynamically engages chromatin in diverse cellular scenarios. In the context of DNA repair, PARP1 becomes enzymatically activat...

biorxiv.org

How do cells tune PRC2 allostery? We find EZH2 Ser21-phos restrains PRC2 adoption of the compact active state. Loss of this restraint promotes H3K27me3, redistributes cPRC1, and impairs differentiation. New bioRxiv with @kasinath-lab.bsky.social & @garcialabms.bsky.social! tinyurl.com/4369kmh2

Does PRC2 interact with RNA or is it an artefact? See our preprint showing how stringent denaturing purifications with spike-in controls support direct interaction between PRC2 and RNA in cells. www.biorxiv.org/content/10.6...

New from the lab: cfDNA provides an unexpected window into telomere chromatin state and genome-wide chromatin changes that accompany telomere shortening, from a blood draw. We hope this opens a path toward monitoring telomere biology disorders with a blood test. www.biorxiv.org/content/10.6...

Out today - structure of the human HIRA histone chaperone complex bound to nucleosomes. Ever wondered how nucleosomes are assembled in the wake of transcription? It takes a 'hulk of a protein complex'. Work by the amazing Wei Tian weetian558.bsky.social. www.biorxiv.org/content/10.6... 🧵

🆕 review with @jpunfried.bsky.social out in Nature SMB. Direct roles of lncRNAs in transcriptional activation. What do we understand about how lncRNAs lure Pol2 and set the stage for RNA production, and what do we still miss? www.nature.com/articles/s41...

Direct roles of long non-coding RNAs in transcription activation - Nature Structural & Molecular Biology

This Review discusses how long noncoding RNAs (lncRNAs) control transcription activation by RNA polymerase II, including how they are produced at active enhancers or chromatin-domain boundaries and ac...

nature.com

New work from Sashi Weerawarana on how TFAM compacts mitochondrial DNA 🧬 TFAM oligomerizes on DNA to form compact, homogeneous higher-order complexes (see beautiful mass photometry data below), that still retain dynamic behavior. Congratulations Sashi and Wei. www.biorxiv.org/content/10.6...

Excited to share our latest work in Molecular Cell: www.cell.com/molecular-ce... We show that PRC1 condensates exclude SWI/SNF from chromatin, revealing a physical mechanism for how opposing regulators compete to control gene expression. Huge thanks to all collaborators and mentors!

Mutual antagonism between PRC1 condensates and SWI/SNF in chromatin regulation

Niekamp et al. show that biomolecular condensates formed by Polycomb repressive complexes can physically restrict access of the activating remodeler SWI/SNF to chromatin. Establishing this barrier dep...

cell.com

Happy to share that David and I have a new review out in @annualreviews.bsky.social of Biochemistry! We break down Pol II pausing, its evidence in vitro/in vivo, and its two key fates which are in kinetic competition: pause release vs premature termination. www.annualreviews.org/content/jour...

The Promoter-Proximal Pause: A Decision Point Governing RNA Polymerase II Fate

A signature feature of transcription on most genes in multicellular animals is that RNA polymerase II (RNAPII) piles up approximately 50 bases downstream of the start site at the promoter-proximal pau...

annualreviews.org

New preprint from our lab! An H3.3 knockout does two things at once: it removes H3.3 from chromatin and destabilizes DAXX. We disentangle those functions and find that DAXX-mediated H3.3 deposition can be uncoupled from ERV silencing. www.biorxiv.org/content/10.6...

🧵 New preprint from our group, in collaboration with the @marcbuhler.bsky.social lab at FMI Basel and the Thalassinos lab at UCL. A long project and a finding we're really pleased with. Thread 👇 www.biorxiv.org/content/10.6...

Incredibly proud to share our new preprint, lead by the Incomparable Rithika Sankar. Here we temporally dissect the role of FACT in mES cells, finding that FACT loss drives progressive deterioration of chromatin architecture, leading to transcriptional collapse. www.biorxiv.org/content/10.6...

I am excited to share a new review @cp-molcell.bsky.social written in collaboration with @tanjamittag.bsky.social , Mikayla Eppert, and Ambuja Navalkar where we review the current evidence for and against the role of density transitions in regulating transcription www.cell.com/molecular-ce...

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...

nature.com

Updates after feedback, so now’s the time to advertise! Our work with the late, great Charles Kirkpatrick, a force in Clin. Immunology for 60 yrs. We found that B cell immunodeficient patients of his had a hypomorphic variant in EZH2 caused by a defect in allostery. www.biorxiv.org/content/10.6...

new paper from the Lai lab! Renfu Shang performs careful mechanistic dissection of miRNA cluster assistance and reveals many insights and surprises to this enigmatic regulatory strategy that gives suboptimal miRNAs a boost. if you love Northerns, you'll ♥️ this! 🧬 genesdev.cshlp.org/content/earl...

Happy to announce the publication of our foray into studying what happens to the transcriptomes of nuclei when cells fuse to form a syncytium. More to follow in the coming few years. One really wonderful thing about the Company of Biologists is that's it's free to publish there for my university!

Epidermal cell fusion promotes the transition from an embryonic to a larval transcriptome in C. elegans

Highlighted Article:eff-1–mediated cell fusion drives transcriptomic progression from an embryonic to larval state in the C. elegans epidermis, without which developmental progression is delayed.

journals.biologists.com

The Reck-Peterson lab at Weill Cornell Medicine is seeking a technician or staff scientist to work on Aspergillus projects. Broad background in fungal biology and techniques required. Bioinformatics skills preferred. Find out more at: reckpetersonlab.org.

Our study with @stadtfeldlab.bsky.social on the dual mechanism by which EHMT2 is repressing totipotency-associated vs lineage-specific loci is now out @emboreports.org. See thread by @cmuyehara.bsky.social who led the study with K Chatterjee. Full article here link.springer.com/article/10.1...

Coordinated repression of totipotency-associated gene loci by histone methyltransferase EHMT2 via LINE1 regulatory elements - EMBO Reports

Mouse embryonic stem cells (mESCs), in addition to differentiating into the three germ layers, can reverse typical developmental trajectories, as exemplified by their ability to de-differentiate into ...

link.springer.com

Chris Uyehara@cmuyehara.bsky.social · 2y ago

Kaushiki and I are excited to share our preprint about fate restriction in pluripotent cells! We show that EHMT2 counteracts the reactivation of clusters of totipotency genes by nucleating heterochromatin domains at LINE-1 repeats. 1/n @efapostolou29.bsky.social and Stadtfeld Labs #DevBio 🧬🖥️

Very happy to share our paper rdcu.be/eUImj out today in @natcellbio.nature.com 🎉🎉🎉 We uncover an unexpected role for endogenous Xist RNA in regulating X-linked genes that escape X-inactivation.

Escape from X inactivation is directly modulated by Xist noncoding RNA

Nature Cell Biology - The authors show that increased Xist RNA levels can induce de novo silencing of genes that normally escape X inactivation. SPEN depletion prevents the silencing of escape...

rdcu.be

Excited to share that this work is now published in its final form! link.springer.com/article/10.1...

TDP-43 directly inhibits mRNA accumulation in neurites through modulation of mRNA stability - The EMBO Journal

The subcellular localization of many mRNAs to neuronal projections allows neurons to efficiently and rapidly react to spatially restricted external cues. However, for most of these RNAs, the mechanism...

link.springer.com

Matthew Taliaferro@jmtali.bsky.social · last yr.

Excited to share our latest work! We asked if and how TDP-43 regulates RNA transport in neurons and if this is misregulated in ALS. We found that it works to keep RNAs *out* of neurites, and that loss of TDP-43 activity results in specific RNAs aberrantly accumulating there.

Took us a bit, but proud of this published version. We now examine the genetic interaction of phosphorylation with oligomerization and where bulk and phospho-Swi6 localize. Wonder if chromatin affinity tuning to enable Suv39 H3K9me3 spreading is a conserved mechanism ? doi.org/10.1093/nar/...

Phosphorylation of HP1/Swi6 relieves competition with Suv39/Clr4 on nucleosomes and enables H3K9 trimethyl spreading

Abstract. Heterochromatin formation in Schizosaccharomyces pombe requires the spreading of histone 3 (H3) Lysine 9 (K9) methylation (me) from nucleation ce

doi.org

Al-Sady lab@al-sadylab.bsky.social · 2y ago

A preprint from the lab led by graduate student Dana R Kennedy. doi.org/10.1101/2024... Over 20 years ago, the Eissenberg lab showed that phosphorylation of HP1 is important for its silencing function. Why? Key observations from our study in fission yeast:

Absolutely thrilled to share the latest work from my lab focused on the variation and evolution of human centromeres among global populations! We assembled 2,110 human centromeres, identifying 226 new major haplotypes and 1,870 α-satellite HOR variants. www.biorxiv.org/content/10.6...

@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...

biorxiv.org

Known for decades: DNA sequence drives nucleosome "rotational positioning" (which face of DNA contacts histones) But: How does this persist when remodelers & transcription constantly mobilize nucleosomes? Our new preprint 1/ : www.biorxiv.org/content/10.6...

The Gonzalez Lab at Columbia University is seeking a scientific leader! Join us in a Research Scientist position, driving single-molecule, structural, and biochemical studies of translation, translational control, and other RNA-based processes. Apply: apply.interfolio.com/176949

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