English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Androgen and glucocorticoid receptor direct distinct transcriptional programs by receptor-specific and shared DNA binding sites

MPS-Authors
/persons/resource/persons145596

Borschiwer,  Marina
Mechanisms of Transcriptional Regulation (Sebastiaan H. Meijsing), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons199348

Bothe,  Melissa
Mechanisms of Transcriptional Regulation (Sebastiaan H. Meijsing), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

Fuchs ,  Alisa
Mechanisms of Transcriptional Regulation (Sebastiaan H. Meijsing), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons73749

Schöne,  Stefanie
Mechanisms of Transcriptional Regulation (Sebastiaan H. Meijsing), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons50428

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

External Ressource
No external resources are shared
Fulltext (public)
Supplementary Material (public)
There is no public supplementary material available
Citation

Borschiwer, M., Bothe, M., Kibar, G., Fuchs, A., Schöne, S., Prekovic, S., et al. (2020). Androgen and glucocorticoid receptor direct distinct transcriptional programs by receptor-specific and shared DNA binding sites. bioRxix (Preprint Sever). doi:10.1101/2020.10.15.340877.


Cite as: http://hdl.handle.net/21.11116/0000-0007-8271-6
Abstract
The glucocorticoid (GR) and androgen (AR) receptors execute unique functions in vivo, yet have nearly identical DNA binding specificities. To identifymechanisms that facilitate functional diversification among these transcription factor paralogs, we studied AR and GR in an equivalent cellular context.Analysis of chromatin and sequence features suggest that divergent binding, and corresponding gene regulation, aredriven by different abilities ofAR and GR to interact with relatively inaccessible chromatin. Divergent genomic binding patterns can also be the results ofsubtle differences in DNA binding preferencebetween AR and GR. Furthermore, the sequence composition of large regions (>10 kb) surrounding selectively occupied binding sites differssignificantly,indicating a role for the sequence environment in selectively guiding AR and GR to distinctbinding sites. The comparison of binding sites that are shared between AR and GR shows that the specificity paradox can also be resolved by differences in the events that occur downstream of receptor binding. Specifically, we find that shared binding sites display receptor-specific enhancer activity, cofactor recruitment and changes in histone modifications.Genomic deletion of shared binding sites demonstrates their contributiontodirecting receptor-specific gene regulation. Together, these data suggest that differencesin genomic occupancy as well as divergencein the events that occur downstream of receptor binding directfunctional diversification among transcription factor paralogs.