English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Genomic dissection of enhancers uncovers principles of combinatorial regulation and dynamic wiring of enhancer-promoter contacts

MPS-Authors
/persons/resource/persons199369

Thormann,  Verena
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/persons188277

Rothkegel,  Maika C.
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/persons194839

Schöpflin,  Robert
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons215729

Glaser,  Laura V.
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/persons73941

Li,  Na
Epigenomics (Ho-Ryun Chung), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons50124

Chung,  Ho-Ryun
Epigenomics (Ho-Ryun Chung), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons50613

Vingron,  Martin
Gene regulation (Martin Vingron), 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)

Thormann.pdf
(Publisher version), 3MB

Supplementary Material (public)
There is no public supplementary material available
Citation

Thormann, V., Rothkegel, M. C., Schöpflin, R., Glaser, L. V., Djuric, P., Li, N., et al. (2018). Genomic dissection of enhancers uncovers principles of combinatorial regulation and dynamic wiring of enhancer-promoter contacts. Nucleic Acids Research (London), 46(6), 2868-2882. doi:10.1093/nar/gky051.


Cite as: http://hdl.handle.net/21.11116/0000-0003-5189-7
Abstract
Genomic binding of transcription factors, like the glucocorticoid receptor (GR), is linked to the regulation of genes. However, as we show here, GR binding is a poor predictor of GR-dependent gene regulation even when taking the 3D organization of the genome into account. To connect GR binding sites to the regulation of genes in the endogenous genomic context, we turned to genome editing. By deleting GR binding sites, individually or in combination, we uncovered how cooperative interactions between binding sites contribute to the regulation of genes. Specifically, for the GR target gene GILZ, we show that the simultaneous presence of a cluster of GR binding sites is required for the activity of an individual enhancer and that the GR-dependent regulation of GILZ depends on multiple GR-bound enhancers. Further, by deleting GR binding sites that are shared between different cell types, we show how cell type-specific genome organization and enhancer-blocking can result in cell type-specific wiring of promoter-enhancer contacts. This rewiring allows an individual GR binding site shared between different cell types to direct the expression of distinct transcripts and thereby contributes to the cell type-specific consequences of glucocorticoid signaling.