🆕 ADVANCE ONLINE 🆕 RESEARCH PAPER: Machine learning analysis of the human initiator region reveals key features of different types of core promoters By Rhyne-Carrigg et al., and James Kadonaga ➡️ https://ow.ly/csE350ZzqTh UC San Diego #transcription #machinelearning

Online Now: Acidic transcription factors position the genome at nuclear speckles through transcription -dependent and -independent mechanisms Online now:

Acidic transcription factors position the genome at nuclear speckles through transcription -dependent and -independent mechanisms

Chaturvedi et al. demonstrate that acidic transcription factors reposition genomic loci to nuclear speckles through both transcription-dependent and transcription-independent mechanisms, revealing that speckle association is actively established by cis-regulatory DNA elements and transcription factor properties rather than arising simply as a consequence of active gene expression.

dlvr.it

Localized mRNAs and protein synthesis in cortical layer 1

Localized mRNAs and protein synthesis in cortical layer 1

Cortical layer 1 is an important site for signal integration and learning-related plasticity. Spanò et al. establish that local protein synthesis characterizes layer 1 and its synapses, and describe the layer 1 local transcriptomes, discovering significant differences from deeper layer transcriptomes and an interesting analogy with hippocampal stratum lacunosum moleculare.

dlvr.it

RNA-binding proteins (RBPs) often bind numerous transcripts - but do they act through a network effect? Our new paper in @plosbiology.org shows that the highly conserved LIN28 RBP controls developmental timing in C. elegans larvae through only two targets. doi.org/10.1371/jour... 1/n

Very happy to see this story finally out (link in comments)! We used low-input Capture Hi-C to profile promoter-anchored chromosomal interactions in Type 3 innate lymphoid cells (ILC3s) - rare tissue-resident lymphocytes that lack antigen receptors and regulate barrier immunity.

MRC Laboratory of Medical Sciences@mrc-lms.bsky.social · 2w ago

New research published today in Nature Genetics uses a technique called mini-Capture Hi-C to map 3D DNA folding in rare ILC3 immune cells, linking 100+ genes to immune disease risk in this cell type 🧬

Genome Research has just announced an exciting call for spatial 'omics related papers! I am thrilled to be co-editing this special issue with Jian Ma (@jianma.bsky.social) and Christina Leslie!

Now online! A domestication-selected enhancer coordinates source-sink balance to improve harvest index and yield in maize

How do transposons jump when they’re released from host control? I babysat two chromosomes for 2 years, making sure they are ok without most piRNAs. Here’s what we found & excited to share my 1st postdoc paper: “piRNA loss unleashes episodic transposition bursts” www.biorxiv.org/content/10.6...

piRNA loss unleashes episodic transposition bursts

In Metazoa, transposon expression is suppressed by the piRNA pathway, and disruption of this pathway leads to rampant transposon expression. However, it remains unclear whether increased transposon ex...

biorxiv.org

Interesting. Full deletion of all introns in yeast was actually my project in the Staley lab, *20 years ago*. I actually found a bunch of phenotypes. We did this in collaboration with the Guthrie lab. www.cell.com/cell/abstrac...

A spliceosome-independent eukaryote generated by complete intron removal

Elimination of all spliceosomal introns reveals a spliceosome-independent eukaryote.

cell.com

"Our goal is to guide the design of experiments that balance biological relevance, sensitivity, and interpretability to ultimately answer a deceptively simple question: What TFs directly regulate the expression of my GOI?" genome.cshlp.org/content/36/3...

Meiotic CENP-C supports #centromere assembly and #kinetochore recruitment in #spermatogenesis. New study form Rachel S. Keegan, Dina Malkeyeva, Meg B. Weever, and Elaine M. Dunleavy @uniofgalway.bsky.social: rupress.org/jcb/article/... #CellCycle #CellDivision #Development #Meiosis #Drosophila

Ribo-Tweezer by @mbarnalab.bsky.social, a modular platform to deplete proteins from mature ribosomes . www.cell.com/molecular-ce... @jakub-zeman.bsky.social and I wrote a Preview on why this helps to turn ribosome heterogeneity into an experimentally testable paradigm www.cell.com/molecular-ce...

Tweezing apart ribosome heterogeneity

In this issue of Molecular Cell, Chen et al. introduce Ribo-Tweezer: a modular platform for conditionally and selectively depleting proteins from mature ribosomes, enabling direct tests of their ribos...

cell.com

In @jcb.org, The discovery of a novel trafficking domain in unorthodox AQP12 by Chauvigné, Cerdà et al. @uab.cat yields insight into the channel’s native membrane function and its molecular regulation in intracellular yolk platelets and pancreatic zymogen granules. rupress.org/jcb/article/...

Why do animals age in such similar ways, yet live for wildly different spans - from days to a century? Our new paper in @NatureAging fits a damage accumulation model across 9 species and finds the knob that best predicts lifespan doi.org/10.1038/s435...

A damage accumulation model identifies distinct aging regimes across species - Nature Aging

Raz and colleagues fit survival data across species to a stochastic model of damage accumulation and removal. They report that damage production rate best predicts lifespan and reveal two distinct agi...

doi.org

Excited to see James' Genome-wide Absolute Quantification of Looping paper out in @natsmb.nature.com : www.nature.com/articles/s41... This has been in collaboration with @lucagiorgetti.bsky.social @leonidmirny.bsky.social @zechnerlab.bsky.social labs. Brief thread below on some key updates

Anders Sejr Hansen@andersshansen.bsky.social · 2y ago

Excited to share James Jusuf's preprint: By integrating Micro-C with SuperRes Live-Imaging we can calibrate genomics&imaging to perform absolute quantification of looping (e.g. this loop is present 3%) We quantify mESC 36k loops: <loops> are generally rare (2.3%) www.biorxiv.org/content/10.1...

Does every enhancer work with every promoter? With @jengreitz.bsky.social and Will Greenleaf, we revisit this long-debated question and resolve an outstanding contradiction in the field. A tour 🧵👇 www.biorxiv.org/content/10.6...

Intrinsic promoter responsiveness dictates sensitivity to transcriptional activation by enhancers

Enhancers activate specific target promoters, but whether intrinsic enhancer-promoter compatibility contributes to this specificity is debated. Recent studies using different reporter assays have reac...

biorxiv.org

If the genome is not a blueprint, what is it? My attempt to unravel this particularly knotty question, in @quantamagazine.bsky.social www.quantamagazine.org/why-the-huma...

Why the Human Genome’s Tangled Physicality May Confound AI | Quanta Magazine

Our genetic heritage is not a blueprint or an algorithm, as many biologists have imagined, but something else entirely.

quantamagazine.org

Developmentally regulated #actin-#microtubule crosstalk in #Drosophila #oogenesis. From Wei-Chien Chou, Brooke M. McCartney and colleagues: rupress.org/jcb/article/... 📕 In our #Microtubules collection: rupress.org/jcb/collecti... #EESMicrotubules

Minibwa is a hybrid of bwa-mem and minimap2 and the successor of bwa-mem for short-read mapping. ~4X/2.5X as fast as bwa-mem/bwa-mem2 for WGS reads at comparable accuracy. Native support of directional bisulfite-seq. Applicable to long reads. Preprint at arxiv.org/abs/2606.15357

🚨Preprint Drop🚨 We are very pleased to release our study on DNA methylation dynamics at enhancers during ESC differentiation! This work was led by Marlet Morales-Franco and Priscillia Lhoumaud 🧵(1/13) www.biorxiv.org/content/10.6...

Dual profiling of DNA modifications with enhancer features during the exit of naive pluripotency

Cis-regulatory elements, such as enhancers, play an essential role in coordinating gene expression programs during cellular transitions. As such, substantial efforts have been made to characterize enh...

biorxiv.org

We just published our new paper about an active Helitron transposon in wheat 🌾🧬 We found that it can be mobilised by heat stress when DNA methylation is reduced. We document its full lifecycle: RNA -> circular DNA -> integration www.nature.com/articles/s41... #TEsky

An active Helitron transposon family in wheat - Nature Plants

Helitrons are a recently identified category of transposons. This study reveals that heat stress combined with reduced DNA methylation can mobilize a Helitron family in wheat. Its mobilization is gene...

nature.com

Exciting breakthrough technology from the lab, now live in @cellcellpress.bsky.social ! Instead of cutting the genome where proteins bind (e.g., Cut&Tag), D&D-seq scars the DNA with a deaminase, allowing single cell genome mapping of TFs and chromatin remodellers!

The demystification of piRNA clusters if you wonder how cells generate piRNAs specifically against transposons & you are looking for a weekend read check out @86dominik.bsky.social's opus magna (or Dominik's great thread) a shared project with the one and only Rippei Hayashi, lab alumnus & friend

Dominik Handler@86dominik.bsky.social · 6mo ago

How does the piRNA pathway solve the self vs. non-self problem? 🧬 Since piRNAs come from single-stranded RNA, how does the cell choose the right ones? For years, "piRNA clusters" were seen as THE privileged source. But are they really special and earmarked for biogenesis? (1/19)

In contrast to prevailing dogma, Bhattacharyya et al. @crg.eu report that procollagen 1 assembles into a liquid condensate within cells, resolving the long-standing problem of how cells accommodate and export high concentrations of these bulky molecules from the ER. rupress.org/jcb/article/...

New paper! How do RNAs "know" where to go inside a cell? We dug into the sequence elements that route RNAs to the right place. It turns out that, in mammals, they're surprisingly massive (>200 nt), multipartite, and wonderfully complicated. 🧵

Finally out in @Cellcellpress! Proteins with long IDRs are prone to misfolding during protein synthesis. This is prevented by mRNA 3′UTRs that act as mRNA-based IDR chaperones. www.cell.com/cell/fulltex...

mRNA 3′ UTRs chaperone intrinsically disordered regions to control protein activity

Highly conserved mRNA 3′ UTRs act as co-translational chaperones for intrinsically disordered regions (IDRs), preventing inter-domain misfolding and enabling biogenesis of fully active proteins.

cell.com

Out now in Science! Our study challenges long-standing assumptions about transcription factor specificity in eukaryotes. Novel single-molecule measurements of TF behavior in living cells reveal an independence of locus-specific binding from DNA sequence recognition.🧵 www.science.org/doi/10.1126/...

Unstructured transcription factor interactions enable emergent specificity

How intrinsically disordered regions (IDRs) shape chromatin binding and nuclear organization of transcription factors (TFs) remains unclear. We used proximity-assisted photoactivation (PAPA), a single...

science.org

New Epigenome Technologies Blog! bit.ly/4tWq8wS "Human Accelerated Regions of the Genome Influence Brain Anatomy via Species-specific Chromatin Looping" Based on a Cell Stem Cell study from Debra L. Silver (Duke University School of Medicine) #EpigenomeTech #Blog #Epigenetics #Chromatin #Looping

So proud to annouce our new paper in Genome Research ! genome.cshlp.org/content/36/5... Here we present scDynaBar, a CRISPR-based molecular recording system that enables the study of dynamic biological processes at single-cell resolution by accumulating and tracking genomic edits over time ⏰ 🧬 📈

Using CRISPR barcoding as a molecular clock to capture dynamic processes at single-cell resolution

Biological processes are inherently dynamic, yet current methods for capturing temporal changes remain limited. Here, we present scDynaBar, a novel approach that combines CRISPR-Cas9 dynamic barcoding with single-cell sequencing. In this system, genetic barcodes gradually accumulate mutations over time; these barcodes are sequenced alongside the transcriptome of individual cells. We propose that the divergence of these barcodes from the original sequence can serve as a record of the timing of cellular events. To demonstrate the potential of this method, we track the transition from a pluripotent state to a two-cell (2C)-like state in mouse embryonic stem cells (mESCs), providing evidence for the transient nature of the 2C-like state. Additionally, our system shows consistent mutation rates across diverse cell types in a mouse gastruloid model, highlighting its applicability to other biological systems. This approach not only improves our ability to study single-cell dynamics but also opens up new possibilities for recording other temporal signals—in other words, using dynamic barcoding as a molecular clock in individual cells.

genome.cshlp.org

Genome Research @genomeresearch.bsky.social · 3mo ago

The new issue of @genomeresearch.bsky.social is now live. Follow the link to new research on single-cell CRISPR barcoding, Drosophila immune response enhancers, and more! tinyurl.com/Genome-Res-3...

“Strikingly, native mRNA sequences are markedly less prone to self-association than matched randomized controls…Similar signatures are observed in abundant human mRNAs, suggesting that evolution has shaped coding sequences to minimize self-association.” 🧪

David Kuster@rnadavid.bsky.social · 3mo ago

Maintaining transcriptome solubility constrains mRNA sequence composition Exploring the propensity for self-association of the transcriptome via RNA–RNA interactions! Amazing preprint by Marco Todisco, Christalyn Ausler and Ankur Jain. www.biorxiv.org/content/10.1...