Andrea Bernardini

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...

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

Cell-type-specific functionality encoded within the intrinsically disordered regions of OCT4 - Nature Communications Here they perform a systematic dissection of OCT4 and reveal how intrinsically disordered regions can be used to serve specific functions during reprogramming and embryonic development. This can be exploited to engineer more efficient and specific reprogramming factors.

Hot off the press!

Cell-type-specific functionality encoded within the intrinsically disordered regions of OCT4

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

All but one bZIP monomer, Jun, has significantly higher affinity for other monomers than its own DNA target, favouring the dimer pathway for target search at equilibrium.

Over 10% of human transcription factors are oligomeric. Stoichiometry might be dialled to modulate transcription. We show CREB searches in DNA mixtures as a dimer, and suggest this might be common amongst other members of the bZIP family which fold on binding DNA.

www.biorxiv.org/content/10.1...

Activity of most genes is controlled by multiple enhancers, but is there activation coordinated? We leveraged Nanopore to identify a specific set of elements that are simultaneously accessible on the same DNA molecules and are coordinated in their activation. www.biorxiv.org/content/10.1...

Affinity-ligand purification of native human low-abundance multi-protein complexes for structure determination In human cells, large multi-protein transcription co-activators, such as chromatin remodelers or histone acetyltransferases, play critical roles in gene-expression regulation and are often implicated ...

Check out our new collaborative preprint about Affinity-ligand purification of native human low-abundance multi-protein complexes doi.org/10.1101/2025...

A novel deep learning-based framework reveals a continuum of chromatin sensitivities across transcription factors The genome-wide binding of many transcription factors (TFs) depends not only on the presence of their recognition motifs, but also on the surrounding chromatin context. This raises the question of how...

Excited to share our latest preprint. www.biorxiv.org/content/10.1.... Lead by Lukas, we investigated multiple ways of assessing a TF's sensitivity to chromatin based on genome-wide binding profiles. The developed methods allowed us to quantify chromatin sensitivity across tested TFs.

Disruption of the SAGA CORE triggers collateral degradation of KAT2A The SAGA transcriptional co-activator complex regulates gene expression through histone acetylation at promoters, mediated by its histone acetyl transferase, KAT2A. While its structure and function ha...

I am pleased to share a new preprint from my postdoc in the @dseruggia.bsky.social lab. We discovered a structural dependency within the CORE module of the transcriptional coactivator SAGA, which regulates the stability of its histone acetyl transferase, KAT2A.
www.biorxiv.org/content/10.1... 1/n

How do chromatin remodelers use #IDRs to find TF binding partners? In our new Molecular Cell paper, we show that β-catenin is an adaptor that links SWI/SNF (cBAF) subunit ARID1A with binding partners via IDR-domain interactions.
www.cell.com/molecular-ce...

Celebrating 10 years of our lab with a new preprint:
www.biorxiv.org/content/10.1...
How does enhancer location within a TAD control transcriptional bursts from a cognate promoter?
Experiments by Jana Tünnermann and modelling by Gregory Roth

Zincore, an atypical coregulator, binds zinc finger transcription factors to control gene expression Zinc finger proteins (ZNFs) are the largest family of transcription factors, yet how they activate gene expression remains unclear. In this study, we identified Zincore, a protein complex consisting o...

In today’s publication in Science we introduce Zincore: a novel protein of QRICH1 and SEPHS1 and functions as a transcriptional coregulator dedicated to zinc finger transcription factors. Here’s how we found it: 🧵 www.science.org/doi/10.1126/... 1/11

Gallo et al. describe NF-YAr, a retroposed copy of the NF-YA transcription factor subunit, in several mammal lineages. Likely expressed in sperm, NF-YAr shows structural changes that suggest altered regulatory function.

🔗 doi.org/10.1093/gbe/evaf071

#genome #evolution #transcription #TEsky

Excited to share my first contribution here at Illumina! We developed PromoterAI, a deep neural network that accurately identifies non-coding promoter variants that disrupt gene expression.🧵 (1/)

Intrinsically disordered regions facilitate Msn2 target search to drive promoter selectivity Transcription factors (TFs) regulate gene expression by binding specific DNA motifs, yet only a fraction of putative sites is occupied in vivo. Intrinsically disordered regions (IDRs) have emerged as ...

1/
New preprint!
How do transcription factors (TFs) use intrinsically disordered regions (IDRs) to find their target sites?

www.biorxiv.org/content/10.1...
#TranscriptionFactors #IDPs #SingleMolecule #Biophysics

I am thrilled to share our preprint where we take advantage of the unique opportunities offered by human blastoids to uncover a human-specific mechanism potentially playing a role in preimplantation 🧵. www.biorxiv.org/content/10.1...

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...
🧵

Dissecting regulatory syntax in human development with scalable multiomics and deep learning Transcription factors (TFs) establish cell identity during development by binding regulatory DNA in a sequence-specific manner, often promoting local chromatin accessibility, and regulating gene expre...

Delighted to share our latest work deciphering the landscape of chromatin accessibility and modeling the DNA sequence syntax rules underlying gene regulation during human fetal development! www.biorxiv.org/content/10.1... Read on for more: 🧵 1/16 #GeneReg 🧬🖥️

Structural basis of human Mediator recruitment by the phosphorylated transcription factor Elk-1 - Nature Communications The Mediator complex subunit MED23 contributes to transcriptional activation by the phosphorylated transcription factor Elk-1, in response to Ras-MAPK signalling. Here, the authors determine a cryo-EM...

Our last contribution is now available.

The first #CryoEM structure of a Mediator subunit (MED23) in complex with the transactivation domain of Elk-1. Unstructured TAD of course, and to spice things up, it's phosphorylation dependent.

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

Congratz Tanja!!

Large language models trained on DNA sequences, also known as genomic language models (gLMs), hold significant potential to advance our understanding of genomes and the interactions between DNA elements that drive complex functions. In this issue of Trends in Genetics, Benegas et al. review key opportunities and challenges for gLMs, outlining important considerations for their development and evaluation to benefit the genomics community. In this image, the two binary strings correspond to reverse-complementary DNA sequences (00 = A, 01 = C, 10 = G, and 11 = T). The connecting rectangles represent “embeddings” learned by gLMs. Illustration by Yun S. Song.

TiG’s April issue is live!

Topics include genomic language models, hyperdivergent regions, meiotic DSBs, cfDNA in pop’n genetics, genital evolution, ‘rulers’ for TSS selection, spatial multiomics in embryos, and more:
www.cell.com/trends/genet...

Thanks to @yun-s-song.bsky.social for the cover!

Having a stressful day? Lay back, crack a beer open and read about how chromatin accessibility responds to perturbations of TF binding at the single molecule level bit.ly/3XQMFxN. I'm incredibly thankful to my PhD mentors @arnaudkr.bsky.social and Judith Zaugg for these super productive years!!

Happy to share the latest story from @arnaudkr.bsky.social's lab @embl.org! With @guidobarzaghi.bsky.social, we used Single Molecule Footprinting to quantify how often chromatin is accessible at enhancers after TF and chromatin environment changes! Check our preprint bit.ly/3XQMFxN + thread ⬇️ 1/11

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...

Read our collaborative paper
@longchrom.bsky.social and @molinalab.bsky.social
showing that disruption of NuA4 and ATAC coactivator complexes cause gene-specific transcript buffering, suggesting that cells dynamically adjust RNA export/degradation to sustain cellular homeostasis.

Intrinsically disordered regions as facilitators of the transcription factor target search - Nature Reviews Genetics Intrinsically disordered domains (IDRs) are increasingly appreciated as important components of protein function. This Perspective discusses the emerging evidence for IDRs from transcription factors a...

Interesting piece on the role of intrinsically disordered regions in #transcriptionfactor specificity, target search etc. ➡️ www.nature.com/articles/s41... #generegulation

What is the multiscale structure of chromatin condensates? How does it shape thermodynamic and material properties?

We address this at near-atomistic resolution🔥🔥🔥 using cryoET (Rosen & Villa labs, led by H Zhou), a new multiscale model (K Russell) and cryoET-guided sims (J Huertas & J Maristany)

Multiscale footprints reveal the organization of cis-regulatory elements www.nature.com/articles/s41...
▶️Footprints of DNA–protein interactions from bulk & single-cell ATAC-seq ⤵️
▶️Deep learning to infer transcription factor and nucleosome binding
▶️Age-associated reduction of nucleosome footprints

Very excited to share our paper on Gene and Transposable Element expression in mammalian preimplantation development, online today! www.cell.com/cell/fulltex...
A short thread to highlight some of our findings 🧵

In a great collaboration with @hummerlab.bsky.social and the Kräusslich lab: HIV capsid doesn't break at the NPC; instead, it cracks open the NPC itself! Details in Cell: authors.elsevier.com/sd/article/S... @mpibp.bsky.social @uniheidelberg.bsky.social A thread below:

Molecular determinants of condensate composition Biomolecular condensates are non-stochiometric assemblies that organize cellular matter in space and time. Despite much work, many questions remain regarding what determines the recruitment and exclus...

New review / perspective with @albertilab-tud.bsky.social on our thoughts on condensate speciality and recruitment, focusing on interplay between site specific and chemically specific interactions

www.cell.com/molecular-ce...