Andrea Bernardini
@bernardini-andrea.bsky.social
Tenure track Researcher
Studying transcription factors & promoters
University of Milan 🇮🇹
previously in Tora's lab, IGBMC 🇫🇷
Studying transcription factors & promoters
University of Milan 🇮🇹
previously in Tora's lab, IGBMC 🇫🇷
Pinned
We wrote an opinion article inspired by the recent exciting reports on the sequence determinants of TSS selection + old observations on TFs activation domains. More posts on this soon!
Q-rich activation domains: flexible ‘rulers’ for transcription start site selection?
www.cell.com/trends/genet...
Q-rich activation domains: flexible ‘rulers’ for transcription start site selection?
www.cell.com/trends/genet...
Q-rich activation domains: flexible ‘rulers’ for transcription start site selection?
Recent findings broadened the function of RNA polymerase II (Pol II) proximal promoter motifs from quantitative regulators of transcription to important determinants of transcription start site (TSS) position. These motifs are recognized by transcription factors (TFs) that we propose to term ‘ruler’ TFs (rTFs), such as NRF1, NF-Y, YY1, ZNF143, BANP, and members of the SP, ETS, and CRE families, sharing as a common feature a glutamine-rich (Q-rich) effector domain also enriched in valine, isoleucine, and threonine (QVIT-rich). We propose that rTFs guide TSS location by constraining the position of the pre-initiation complex (PIC) during its promoter recognition phase through a specialized, and still enigmatic, class of activation domains.
www.cell.com
Brief thread on our opinion article "Q-rich activation domains: flexible ‘rulers’ for transcription start site selection?". Transcription people are surely aware of the important reports on the DNA sequence determinants of start site (TSS) selection in the human genome that came out this year. 1/15
Reposted by Andrea Bernardini
We are pleased to announce a new preprint by @mlweilert.bsky.social: “Widespread low-affinity motifs enhance chromatin accessibility and regulatory potential in mESCs” (www.biorxiv.org/content/10.1...). See summary and longer recap below:
(TLDR; low-affinity motifs matter as pioneers!)
(TLDR; low-affinity motifs matter as pioneers!)
Widespread low-affinity motifs enhance chromatin accessibility and regulatory potential in mESCs
Low-affinity transcription factor (TF) motifs are an important element of the cis-regulatory code, yet they are notoriously difficult to map and mechanistically incompletely understood, limiting our a...
www.biorxiv.org
November 19, 2025 at 8:57 PM
We are pleased to announce a new preprint by @mlweilert.bsky.social: “Widespread low-affinity motifs enhance chromatin accessibility and regulatory potential in mESCs” (www.biorxiv.org/content/10.1...). See summary and longer recap below:
(TLDR; low-affinity motifs matter as pioneers!)
(TLDR; low-affinity motifs matter as pioneers!)
Reposted by Andrea Bernardini
Our latest paper has just been published in Cell!
doi.org/10.1016/j.ce...
We developed a new method called MCC ultra, which allows 3D chromatin structure to be visualised with a 1 base pair pixel size.
doi.org/10.1016/j.ce...
We developed a new method called MCC ultra, which allows 3D chromatin structure to be visualised with a 1 base pair pixel size.
November 5, 2025 at 5:20 PM
Our latest paper has just been published in Cell!
doi.org/10.1016/j.ce...
We developed a new method called MCC ultra, which allows 3D chromatin structure to be visualised with a 1 base pair pixel size.
doi.org/10.1016/j.ce...
We developed a new method called MCC ultra, which allows 3D chromatin structure to be visualised with a 1 base pair pixel size.
Reposted by Andrea Bernardini
What is a promoter? And how does it work?
We very happy to share our latest work trying to understand enhancer-promoter compatibility.
I am very excited about the results of @blanka-majchrzycka.bsky.social, which changed the way I think about promoters
www.biorxiv.org/content/10.1...
We very happy to share our latest work trying to understand enhancer-promoter compatibility.
I am very excited about the results of @blanka-majchrzycka.bsky.social, which changed the way I think about promoters
www.biorxiv.org/content/10.1...
Enhancer-promoter compatibility is mediated by the promoter-proximal region
Gene promoters induce transcription in response to distal enhancers. How enhancers specifically activate their target promoter while bypassing other promoters remains unclear. Here, we find that the p...
www.biorxiv.org
October 16, 2025 at 3:06 PM
What is a promoter? And how does it work?
We very happy to share our latest work trying to understand enhancer-promoter compatibility.
I am very excited about the results of @blanka-majchrzycka.bsky.social, which changed the way I think about promoters
www.biorxiv.org/content/10.1...
We very happy to share our latest work trying to understand enhancer-promoter compatibility.
I am very excited about the results of @blanka-majchrzycka.bsky.social, which changed the way I think about promoters
www.biorxiv.org/content/10.1...
Reposted by Andrea Bernardini
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
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...
www.biorxiv.org
October 7, 2025 at 7:43 PM
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
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
Reposted by Andrea Bernardini
Hot off the press!
Cell-type-specific functionality encoded within the intrinsically disordered regions of OCT4
www.nature.com/articles/s41...
Cell-type-specific functionality encoded within the intrinsically disordered regions of OCT4
www.nature.com/articles/s41...
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.
www.nature.com
September 30, 2025 at 4:16 PM
Hot off the press!
Cell-type-specific functionality encoded within the intrinsically disordered regions of OCT4
www.nature.com/articles/s41...
Cell-type-specific functionality encoded within the intrinsically disordered regions of OCT4
www.nature.com/articles/s41...
Reposted by Andrea Bernardini
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...
www.biorxiv.org/content/10.1...
September 8, 2025 at 9:36 AM
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...
www.biorxiv.org/content/10.1...
Reposted by Andrea Bernardini
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...
August 18, 2025 at 12:23 PM
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...
Reposted by Andrea Bernardini
Check out our new collaborative preprint about Affinity-ligand purification of native human low-abundance multi-protein complexes doi.org/10.1101/2025...
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 ...
doi.org
August 12, 2025 at 7:30 AM
Check out our new collaborative preprint about Affinity-ligand purification of native human low-abundance multi-protein complexes doi.org/10.1101/2025...
Reposted by Andrea Bernardini
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.
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...
www.biorxiv.org
August 12, 2025 at 8:32 AM
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.
Reposted by Andrea Bernardini
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
www.biorxiv.org/content/10.1... 1/n
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...
www.biorxiv.org
August 1, 2025 at 5:43 PM
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
www.biorxiv.org/content/10.1... 1/n
Reposted by Andrea Bernardini
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...
www.cell.com/molecular-ce...
July 22, 2025 at 6:42 PM
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...
www.cell.com/molecular-ce...
Reposted by Andrea Bernardini
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
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
March 29, 2025 at 12:46 PM
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
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
Reposted by Andrea Bernardini
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
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...
www.science.org
July 4, 2025 at 11:00 AM
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
Reposted by Andrea Bernardini
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
🔗 doi.org/10.1093/gbe/evaf071
#genome #evolution #transcription #TEsky
May 27, 2025 at 8:10 AM
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
🔗 doi.org/10.1093/gbe/evaf071
#genome #evolution #transcription #TEsky
Reposted by Andrea Bernardini
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/)
May 29, 2025 at 11:57 PM
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/)
Reposted by Andrea Bernardini
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
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
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 ...
www.biorxiv.org
May 27, 2025 at 10:11 PM
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
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
Reposted by Andrea Bernardini
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...
May 12, 2025 at 8:25 PM
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...
Reposted by Andrea Bernardini
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...
🧵
🧬🩸 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...
🧵
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...
www.cell.com
May 8, 2025 at 4:07 PM
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...
🧵
🧬🩸 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...
🧵
Reposted by Andrea Bernardini
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 🧬🖥️
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...
www.biorxiv.org
May 3, 2025 at 6:27 PM
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 🧬🖥️
Reposted by Andrea Bernardini
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...
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...
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...
www.nature.com
April 23, 2025 at 3:48 AM
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...
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...
Reposted by Andrea Bernardini
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!
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!
April 8, 2025 at 1:30 PM
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!
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!
Reposted by Andrea Bernardini
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!!
April 8, 2025 at 3:41 PM
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!!
Reposted by Andrea Bernardini
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
April 8, 2025 at 1:52 PM
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
Reposted by Andrea Bernardini
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...
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...
March 26, 2025 at 5:11 PM
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...
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...