Gene regulatory networks: from correlative models to causal explanations Nature Reviews Genetics - In this Perspective, Maizels and Briscoe discuss the limitations of current models of gene regulatory networks and outline solutions to harness data abundance without...

New Perspective form Rory Maizels & me: "Gene regulatory networks: from correlative models to causal explanations"

Gene regulatory networks are supposed to give us mechanistic explanations of development, so why are we drowning in 'hairballs' of statistical correlations?

rdcu.be/e7zx7

We wrote a perspective "How to build the regulatory genome: a constructionist guide to the cis-regulatory code", out in Development yesterday. Title says it all. Find it here:

journals.biologists.com/dev/article/...

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...

☕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 inhibitors in mixed-lineage leukaemia.
bit.ly/46MZ3Di

Pleased to share the final version of this behemoth of a paper, now finally published. I guess I can retire now?
www.nature.com/articles/s41...

More functional data, many thousands of words removed, and a few other updates from last year's preprint.

Intelligence Evolved at Least Twice in Vertebrate Animals | Quanta Magazine Complex neural circuits likely arose independently in birds and mammals, suggesting that vertebrates evolved intelligence multiple times.

“A bird with a 10-gram brain is doing pretty much the same as a chimp with a 400-gram brain,” said Onur Güntürkün, who studies brain structures at Ruhr University Bochum in Germany. “How is it possible?”

A Naïve RNA Sampling Core Enables Adaptive piRNA Specificity Against Transposable Elements https://www.biorxiv.org/content/10.64898/2026.02.07.704324v1

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...

H3K79me2/3 is sufficient to antagonise PRC1 www.nature.com/articles/s41...

Congrats also to the @davidovichlab.bsky.social who i forgot to mention in the original post!

i think it has major implications for the role of chromatin in cell type stability, and even for developmental tempo, as the modification deposited by DOT1L is only diluted through cell division. This provides a means to directly link cell state changes with division rate in development.

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/articles/s41...

happy i could be a part of this paper from the Gilan lab out now. Along with many other things, it provides strong evidence of chromatin memory for gene activation, and suggests that DOT1L is the missing link balancing the fast and slow arms of the MLL/Polycomb axis

Construction of complex and diverse DNA sequences using DNA three-way junctions - Nature Sidewinder enables high-fidelity DNA assembly by separating the information that guides assembly from the final assembled sequence.

Nature research paper: Construction of complex and diverse DNA sequences using DNA three-way junctions

go.nature.com/4qu2ExZ

Hierarchical buffering of cellular RNA polymerase II pools maintains transcriptional homeostasis RNA polymerase II (Pol II) abundance and transcriptional output are coordinated across diverse conditions to maintain mRNA homeostasis. To determine whether Pol II acts as a limiting factor for transc...

What happens when you suddenly remove half of an essential enzyme from cells? 🤔

We watched in real-time as cells deploy multiple backup strategies to buffer against changes in RNA Pol II abundance.

Our lab's new preprint 👇

bit.ly/4pyPgax

And also taf1 to some extent

It's nice to see this is consistent with what we found in our paper where TCT promoters have increased dependence on taf2,7 and 8 and less dependence on tbp than TATA promoters www.nature.com/articles/s41...

Can't believe it's that time of year - registration already open for next year's Transcription & Chromatin meeting. Almost half the talks are selected from the abstracts, so register soon before it fills up. This is a very lively meeting, with plenty of time to discuss over dinner & at the bar

Billions going unspent from Australia’s $24b medical research fund Costings commissioned by independent MP Monique Ryan reveal the government could double how much funding it gives to innovative health research each year.

www.theage.com.au/politics/fed...

18/ At large genomic distance, long encounters (=the important ones) are only due to loop extrusion; but at short genomic distance they can also be due to random collisions. This is why enhancers are no sensitive to loss of extrusion when they are close, but sensitive when they are far!

Really excited to share our latest work led by @mattiaubertini.bsky.social and @nesslfy.bsky.social: we report that cohesin loop extrusion creates rare but long-lived encounters between genomic sequences which underlie efficient enhancer-promoter communication.
www.biorxiv.org/content/10.1...
A🧵👇

We are looking for a student to continue our work on chromatin evolution:
www.nature.com/articles/s41...
www.biorxiv.org/content/10.1...

The project with @seanamontgomery.bsky.social will focus on chromatin state readers across eukaryotes.

More info: recruitment.crg.eu/content/jobs...

New preprint from the lab 🎉 on the evolution of gene regulatory network complexity, where we tested whether sexual recombination promotes more complex GRNs using biochemically-inspired evolutionary simulations 🧐. Bluetorial from 1st author @chapelmadison.bsky.social 👇

Regulation of somatic hypermutation by higher-order chromatin structure Schoeberl et al. employ Tri-C to unravel the higher-order chromatin architecture underpinning the co-transcriptional mutagenesis of immunoglobulin genes during antibody maturation in human B cells. They provide evidence that antibody maturation occurs within a dynamic multiway hub wherein transcription and mutation of different genes occur non-competitively.

Online Now: Regulation of somatic hypermutation by higher-order chromatin structure Online now:

A cellular entity retaining only its replicative core: Hidden archaeal lineage with an ultra-reduced genome Defining the minimal genetic requirements for cellular life remains a fundamental question in biology. Genomic exploration continually reveals novel microbial lineages, often exhibiting extreme genome...

So cool, a novel archaeon with a super small genome and no metabolic genes!
"An unprecedented level of metabolic dependence on a host, a condition that challenges the functional distinctions between minimal cellular life and viruses."
www.biorxiv.org/content/10.1...

Many cells during development are exposed to caspase activation and yet survive. Why some die and not others ? We found out that the memory of previous caspase activation bias significantly later death comitment and bias death distribution and single cell decision
www.biorxiv.org/content/10.1...

Clonal tracing with somatic epimutations reveals dynamics of blood ageing - Nature The discovery that DNA methylation of different CpG sites can serve as digital barcodes of clonal identity led to the development of EPI-Clone, an algorithm that enables single-cell lineage tracing th...

Out @nature.com: Clonal tracing with somatic epimutations

🧬 Single cell methylome encodes cell state & clonal identity

🔨 EPI-Clone reads out both (+mutations, +RNA) at scale

🩸 Clonal expansions of HSCs are universal from age 50, not driven by CH mutations

doi.org/10.1038/s415...
🧵

Design principles of cell-state-specific enhancers in hematopoiesis Screen of minimalistic enhancers in blood progenitor cells demonstrates widespread dual activator-repressor function of transcription factors (TFs) and enables the model-guided design of cell-state-sp...

Out in Cell @cp-cell.bsky.social: Design principles of cell-state-specific enhancers in hematopoiesis
🧬🩸 screen of fully synthetic enhancers in blood progenitors
🤖 AI that creates new cell state specific enhancers
🔍 negative synergies between TFs lead to specificity!
www.cell.com/cell/fulltex...
🧵

🐛🕷️🕸️ @science.org Hawaiian caterpillar patrols spiderwebs camouflaged in insect prey’s body parts | Science www.science.org/doi/10.1126/... #entomology

DNA-guided transcription factor interactions extend human gene regulatory code - Nature A large-scale analysis of DNA-bound transcription factors (TFs) shows how the presence of DNA markedly affects the landscape of TF interactions, and identifies composite motifs that are recognized by complexes of TFs rather than by individual ones.

Nature research paper: DNA-guided transcription factor interactions extend human gene regulatory code

https://go.nature.com/4j13XRc

DNA-guided transcription factor interactions extend human gene regulatory code - Nature A large-scale analysis of DNA-bound transcription factors (TFs) shows how the presence of DNA markedly affects the landscape of TF interactions, and identifies composite motifs that are recognized by ...

www.nature.com/articles/s41...

our work on the molecular differences between transcription factor isoforms is out now in Molecular Cell!

key point: 2/3rds of TF isos differ in properties like DNA binding & transcriptional activity

many are "negative regulators" & misexpressed in cancer

www.sciencedirect.com/science/arti...

1/ H3K27me3 mimicry has repeatedly emerged through evolution, but what's the physiological relevance?

We show that JARID2 and PALI1 mimic H3K27me3 to antagonise PRC2 in vivo and restrict the spread of Polycomb domains.
🧵
www.biorxiv.org/content/10.1...