English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Preformed Chromatin Topology Assists Transcriptional Robustness of Shh during Limb Development

Paliou, C., Guckelberger, P., Schöpflin, R., Heinrich, V., Esposito, A., Chiariello, A. M., et al. (2019). Preformed Chromatin Topology Assists Transcriptional Robustness of Shh during Limb Development. bioRxiv (Preprint Server), 2019: 528877. doi:10.1101/528877 (bioRxiv).

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0003-1B8A-4 Version Permalink: http://hdl.handle.net/21.11116/0000-0004-98E3-0
Genre: Journal Article

Files

show Files
hide Files
:
Paliou.pdf (Preprint), 2MB
Name:
Paliou.pdf
Description:
bioRxiv
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2019, The authors.
:
Paliou2019.pdf (Publisher version), 3MB
Name:
Paliou2019.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2019 National Academy of Sciences
License:
-
:
pnas.1900672116.sapp.pdf (Supplementary material), 3MB
Name:
pnas.1900672116.sapp.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2019 National Academy of Sciences
License:
-
:
pnas.1900672116.sm01.mp4 (Supplementary material), 2MB
Name:
pnas.1900672116.sm01.mp4
Description:
-
Visibility:
Public
MIME-Type / Checksum:
video/mp4 / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2019 National Academy of Sciences
License:
-

Locators

show

Creators

show
hide
 Creators:
Paliou, Christina1, Author              
Guckelberger, Philine , Author
Schöpflin, Robert1, Author              
Heinrich, Verena2, Author              
Esposito, Andrea, Author
Chiariello, Andrea M. , Author
Bianco, Simona , Author
Annunziatella, Carlo , Author
Helmuth, Johannes, Author
Haas, Stefan3, Author              
Jerković, Ivana, Author
Brieske, Norbert1, Author              
Wittler, Lars4, Author              
Timmermann, Bernd5, Author              
Nicodemi, Mario , Author
Vingron, Martin2, Author              
Mundlos, Stefan1, Author              
Andrey, Guillaume , Author
Affiliations:
1Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              
2Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479639              
3Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433547              
4Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433548              
5Sequencing (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479670              

Content

show
hide
Free keywords: 3D genome; development; gene regulation; genetics; limb
 Abstract: Long-range gene regulation involves physical proximity between enhancers and promoters to generate precise patterns of gene expression in space and time. However, in some cases proximity coincides with gene activation, whereas in others preformed topologies already exist before activation. In this study, we investigate the preformed configuration underlying the regulation of the Shh gene by its unique limb enhancer, the ZRS, in vivo during mouse development. Abrogating the constitutive transcription covering the ZRS region led to a shift within the Shh-ZRS contacts and a moderate reduction in Shh transcription. Deletion of the CTCF binding sites around the ZRS resulted in a loss of the Shh-ZRS preformed interaction and a 50% decrease in Shh expression but no phenotype, suggesting an additional, CTCF-independent mechanism of promoter-enhancer communication. This residual activity, however, was diminished by combining the loss of CTCF binding with a hypomorphic ZRS allele resulting in severe Shh loss-of-function and digit agenesis. Our results indicate that the preformed chromatin structure of the Shh locus is sustained by multiple components and acts to reinforce enhancer-promoter communication for robust transcription.

Details

show
hide
Language(s): eng - English
 Dates: 2019-01-232019-06-18
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: bioRxiv (Preprint Server)
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Cold Spring Harbor, NY : Cold Spring Harbor Laboratory
Pages: - Volume / Issue: 2019 Sequence Number: 528877 Start / End Page: - Identifier: -

Source 2

show
hide
Title: Proceedings of the National Academy of Sciences of the United States of America
  Other : Proc. Acad. Sci. USA
  Other : Proc. Acad. Sci. U.S.A.
  Other : Proceedings of the National Academy of Sciences of the USA
  Abbreviation : PNAS
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Washington, D.C. : National Academy of Sciences
Pages: 10 Volume / Issue: 116 (25) Sequence Number: - Start / End Page: 12390 - 12399 Identifier: ISSN: 0027-8424
CoNE: https://pure.mpg.de/cone/journals/resource/954925427230