Dynamic 3D chromatin architecture determines enhancer specificity and 
morphogenetic identity in limb development

Kragesteen , Bjørt K.; Spielmann, Malte; Paliou, Christina; Heinrich, Verena; Schöpflin, Robert; Esposito, Andrea; Annunziatella, Carlo; Bianco , Simona; Chiariello, Andrea M.; Jerković , Ivana; Harabula, Izabela; Guckelberger, Philine; Pechstein, Michael; Wittler, Lars; Chan, Wing-Lee; Franke, Martin; Lupiáñez , Darío G.; Kraft, Katerina; Timmermann, Bernd; Vingron, Martin; Visel, Axel; Nicodemi, Mario; Mundlos, Stefan; Andrey, Guillaume

doi:10.1038/s41588-018-0221-x

Datensatz

DATENSATZ AKTIONENEXPORT

Zur Ablage hinzufügen

Lokale TagsFreigabegeschichteDetailsÜbersicht

Freigegeben

Zeitschriftenartikel

Dynamic 3D chromatin architecture determines enhancer specificity and morphogenetic identity in limb development

MPG-Autoren

Kragesteen , Bjørt K.
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons50565

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

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

/persons/resource/persons179829

Heinrich, Verena
Gene regulation (Martin Vingron), 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;
Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

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

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

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

/persons/resource/persons50647

Wittler, Lars
Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society;

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

Lupiáñez , Darío G.
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons73905

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

/persons/resource/persons50598

Timmermann, Bernd
Sequencing (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), 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/persons50437

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

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

Externe Ressourcen

Es sind keine externen Ressourcen hinterlegt

Volltexte (beschränkter Zugriff)

Für Ihren IP-Bereich sind aktuell keine Volltexte freigegeben.

Volltexte (frei zugänglich)

Kragesteen.pdf
(Verlagsversion), 5MB

Ergänzendes Material (frei zugänglich)

Kragesteen _Suppl.Text&Figures.pdf
(Ergänzendes Material), 3MB

Kregesteen_Suppl.Table1.xlsx
(Ergänzendes Material), 10KB

Kregesteen_Suppl.Table2.xlsx
(Ergänzendes Material), 14KB

Zitation

Kragesteen, B. K., Spielmann, M., Paliou, C., Heinrich, V., Schöpflin, R., Esposito, A., et al. (2018). Dynamic 3D chromatin architecture determines enhancer specificity and morphogenetic identity in limb development. Nature Genetics, 50(10), 1463-1473. doi:10.1038/s41588-018-0221-x.

Zitierlink: https://hdl.handle.net/21.11116/0000-0002-7E55-2

Zusammenfassung

The regulatory specificity of enhancers and their interaction with gene promoters is thought to be controlled by their sequence and the binding of transcription factors. By studying Pitx1, a regulator of hindlimb development, we show that dynamic changes in chromatin conformation can restrict the activity of enhancers. Inconsistent with its hindlimb-restricted expression, Pitx1 is controlled by an enhancer (Pen) that shows activity in forelimbs and hindlimbs. By Capture Hi-C and three-dimensional modeling of the locus, we demonstrate that forelimbs and hindlimbs have fundamentally different chromatin configurations, whereby Pen and Pitx1 interact in hindlimbs and are physically separated in forelimbs. Structural variants can convert the inactive into the active conformation, thereby inducing Pitx1 misexpression in forelimbs, causing partial arm-to-leg transformation in mice and humans. Thus, tissue-specific three-dimensional chromatin conformation can contribute to enhancer activity and specificity in vivo and its disturbance can result in gene misexpression and disease.