Nitzan Gonen

What happens when you change the promoter of my favorite gene? Sox9?

Reporter CRISPR screens decipher cis-regulatory and trans-regulatory principles at the Xist locus - Nature Structural & Molecular Biology Here Schwämmle et al. develop CRISPR reporter screens to map transcription-factor-regulatory element interactions at the Xist locus, revealing a two-step mechanism integrating developmental and X-dosage signals to initiate X-chromosome inactivation.

⚠️ Paper alert: Using a novel CRISPR screening approach, we mapped the entire regulatory network controlling Xist—key for X-chromosome inactivation.
👉 We discover how sex and development signals are decoded at a single gene locus.
www.nature.com/articles/s41...
👇 Bluetorial

📢To all the sex determination lovers! 📢

Get ready for the 10th International Symposium on the Biology of Vertabrate Sex Determination (VSD).

We exchange the nostalgic Hawaii beaches with the gorgeous Crete beaches 🏖!
The meeting will take place on 23-27 March 2026.

biology-of-vsd.my.canva.site

Publishing an exciting paper and getting an ISF grant, both at the same week, is a good justification of Pizza and Prosecco in the middle of the day! 🍾🥂 Huge congrats to Isabelle, Meshi and Elisheva for this superb publication 💪

Thank you so much Sandra 🙏

Thanks dear and thank you for all the help and advice 😘

Thanks Rod 🙏

Thanks so much Jen!!

10/n And like any good paper, this is just the beginning for many cool followup projects where we delve into the mechanism and functional exploration of candidate enhancers. Cool stuff in the pipe, stay tuned!!!
We want to thank the reviewers for the constructive advice 🙏

9/n Last but not least, we performed ATAC TFs footprinting to look for TF occupancy on the regulatory regions. While we found the usual suspects in Sertoli cells: SOX, DMRT, NR5A1, the top occupied motif in granulosa cells was that of Lhx9/Emx2!!

8/n In addition, we conducted computational linkage analysis linking genes to their regulatory elements in a positive (enhancer) or negative manner (silencer).

7/n We then applied Promoter Capture HiC on E13.5 Sertoli and granulosa cells and were able to identify physical proximity between enhancers and their target genes. This was done with the superb Lera Malysheva.

6/n We then focused on regulatory elements. We identified numerous regulatory elements that are specific to the sex (testis/ ovaries) or to the developmental time

5/n We employed ATAC-seq and RNA-seq on these cells to identify their gene expression and functional regulatory elements. We provide a cool tool that enables you to track the expression of your gene of interest. Check this out:
4ljrl2-roni-weiss.shinyapps.io/tpm_allgenes/

4/n To start looking at that we started a project 5 years ago that came into completion now. We used existing and new transgenic mouse lines that enable u to purify Sertoli and granulosa cells during 4 key time pints in which the sex is being determined (E11.5-15.5)

a man in a suit and tie is standing in front of a window with blinds ALT: a man in a suit and tie is standing in front of a window with blinds

3/n So, I believe that a lot of the action is mediated via the non-coding parts of the genome, but where exactly??? it is 98% of the genome!

2/n So you all know that I am obsessed about my precious Enh13, deletions/duplications of which lead to XY and XX sex reversal in mice and human. And, we know that most DSD patients fail to receive genetic diagnosis even after whole exome sequencing.

The gene regulatory landscape driving mouse gonadal supporting cell differentiation Multiomics analysis revealed the regulatory elements and transcription factors responsible for gonadal sex determination.

1/n Very excited to share our recent paper published on
@ScienceAdvances
where we dissect the gene regulatory landscape guiding mouse sex determination!
science.org/doi/10.1126/...
A huge well done to @IsabelleStevant.genomic.social.ap.brid.gy, Meshi and Elisheva who spearhead this project!

Congrats Vicki, super interesting!

AlphaGenome: AI for better understanding the genome Introducing a new, unifying DNA sequence model that advances regulatory variant-effect prediction and promises to shed new light on genome function — now available via API.

Alpha Genome by DeepMind...
Will it be as good as AlphaFold??
deepmind.google/discover/blo...

Male mice can grow ovaries if their pregnant mums are iron deficient The study is the first to show that low iron levels can affect fetal sexual development.

Male mouse fetuses can develop female organs in utero if their mother is iron deficient during pregnancy

https://go.nature.com/43N7f4s

Maternal iron deficiency causes male-to-female sex reversal in mouse embryos - Nature Iron-deficient conditions in pregnant mice can cause XY mouse embryos to develop female rather than male genitalia, revealing that iron metabolism has a role in determining male sex in mice.

One of the coolest papers in the field of sex determination!

It is the first evidence that environmental aspects can affect mammalian sex determination!!

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

Conservation of regulatory elements with highly diverged sequences across large evolutionary distances Nature Genetics - Combining functional genomic data from mouse and chicken with a synteny-based strategy identifies positionally conserved cis-regulatory elements in the absence of direct sequence...

How to find Evolutionary Conserved Enhancers in 2025? 🐣-🐭
Check out our paper - fresh off the press!!!
We find widespread functional conservation of enhancers in absence of sequence homology
Including: a bioinformatic tool to map sequence-diverged enhancers!
rdcu.be/enVDN
github.com/tobiaszehnde...

Had the best time in Geneva, visiting my friend and collaborator Serge Nef.
I saw the beautiful city of Geneva, gave a seminar at the Medicine Faculty of Geneva University and met many brilliant scientists!!
Heading next to Zurich for the #TT2025 meeting to hear about transgenic mice technologies!

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 ...

A tour de force study from Taipale&Yin labs. It expands the vocabulary of the Regulatory Code by adding 1131 TF:TF composite motifs that are different from the individual TF motifs. The new composite motifs are enriched in cell-type specific elements and active in vivo
www.nature.com/articles/s41...

Hormone-Free Male Birth Control Pill Enters Clinical Trials For The First Time A hormone-free male birth control pill is undergoing clinical testing for the first time ever.

Very cool and about time!

www.sciencealert.com/hormone-free...

Joy (2024) ⭐ 7.1 | Biography, Drama, History 1h 55m | PG-13

Highly recommend all scientist to watch the movie Joy on Netflix! It tells the story of IVF and the birth of Louise Joy Brown in 1978 and all the scientific endeavour behind. Millions of failures for 1 amazing success! This is what science is all about
m.imdb.com/title/tt1024...

bioRxiv Genomics on X: "Exonic enhancers are a widespread class of dual-function regulatory elements https://t.co/Ho0TdalAsu #biorxiv_genomic" / X Exonic enhancers are a widespread class of dual-function regulatory elements https://t.co/Ho0TdalAsu #biorxiv_genomic

Exonic enhancers are a widespread class of dual-function regulatory elements

x.com/biorxiv_geno...

Among the fun parts of being a scientist is going to conferences!!
A first time in Washington D.C where I will present our work at the #asa_ica25conf tomorrow. Come and hear me if you are here