English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Preprint

Reporter CRISPR screens decipher cis- and trans-regulatory principles at the Xist locus

MPS-Authors
/persons/resource/persons232044

Schwaemmle,  Till       
Systems Epigenetics (Edda G. Schulz), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons244882

Noviello,  Gemma       
Systems Epigenetics (Edda G. Schulz), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons276130

Kanata,  Eleni       
Systems Epigenetics (Edda G. Schulz), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons285914

Froehlich,  Jonathan J.       
Systems Epigenetics (Edda G. Schulz), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons199348

Bothe,  Melissa
Systems Epigenetics (Edda G. Schulz), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons244983

Altay,  Aybuge       
Transcriptional Regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons285916

Scouarnec,  Jade
Systems Epigenetics (Edda G. Schulz), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons295808

Feng,  Vivi-Yun       
Systems Epigenetics (Edda G. Schulz), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons50613

Vingron,  Martin       
Transcriptional Regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons145411

Schulz,  Edda G.       
Systems Epigenetics (Edda G. Schulz), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
Supplementary Material (public)
There is no public supplementary material available
Citation

Schwaemmle, T., Noviello, G., Kanata, E., Froehlich, J. J., Bothe, M., Altay, A., et al. (2024). Reporter CRISPR screens decipher cis- and trans-regulatory principles at the Xist locus. bioRxiv. doi:10.1101/2024.10.08.617282.


Cite as: https://hdl.handle.net/21.11116/0000-000F-EE0E-7
Abstract
Developmental genes are controlled by an ensemble of cis-acting regulatory elements (REs), which in turn respond to multiple trans-acting transcription factors (TFs). Understanding how a cis-regulatory landscape integrates information from many dynamically expressed TFs has remained a challenge. We develop a combined CRISPR-screening approach using endogenous RNA and RE-reporters as readouts. Applied to the Xist locus, crucial for X-chromosome inactivation in females, this method allows us to comprehensively identify Xist-controlling TFs and map their TF-RE wiring. We find a group of transiently expressed TFs that regulate proximal REs, driving the binary activation of Xist expression. These basal activators are more highly expressed in cells with two X chromosomes, potentially driving female-specific Xist upregulation. A second set of developmental TFs is upregulated later during differentiation and targets distal REs. This regulatory axis is crucial to achieve high levels of Xist RNA, which is necessary for X-chromosome inactivation. Our findings support a model for developmental gene regulation in which factors targeting proximal REs drive binary ON-OFF decisions, while factors interacting with distal REs control the transcription output.