English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Enhancer hijacking determines extrachromosomal circular MYCN amplicon architecture in neuroblastoma

Helmsauer, K., Valieva, M., Ali, S., Chamorro González, R., Schöpflin, R., Röefzaad, C., et al. (2020). Enhancer hijacking determines extrachromosomal circular MYCN amplicon architecture in neuroblastoma. Nature Communications, 2020(11): 11:5823. doi:10.1038/s41467-020-19452-y.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0007-ABAE-5 Version Permalink: http://hdl.handle.net/21.11116/0000-0007-ABAF-4
Genre: Journal Article

Files

show Files
hide Files
:
Helmsauer_2020.pdf (Publisher version), 3MB
Name:
Helmsauer_2020.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2020, The Author(s)

Locators

show

Creators

show
hide
 Creators:
Helmsauer, Konstantin , Author
Valieva, Maria1, Author              
Ali , Salaheddine 1, Author
Chamorro González, Rocío , Author
Schöpflin, Robert1, Author              
Röefzaad, Claudia , Author
Bei, Yi, Author
Dorado Garcia, Heathcliff , Author
Rodriguez-Fos, Elias , Author
Puiggròs, Montserrat , Author
Kasack, Katharina , Author
Haase, Kerstin, Author
Keskeny, Csilla , Author
Chen, Celine Y. , Author
Kuschel, Luis P. , Author
Euskirchen, Philipp , Author
Heinrich, Verena, Author
Robson, Michael1, Author              
Rosswog, Carolina , Author
Toedling, Joern , Author
Szymansky, Annabell , AuthorHertwig, Falk, AuthorFischer, Matthias , AuthorTorrents, David , AuthorEggert, Angelika , AuthorSchulte, Johannes H. , AuthorMundlos, Stefan1, 2, 3, Author              Henssen, Anton G. , AuthorKoche, Richard P. , Author more..
Affiliations:
1Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              
2Institute for Medical and Human Genetics, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany, ou_persistent22              
3Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany, ou_persistent22              

Content

show
hide
Free keywords: -
 Abstract: MYCN amplification drives one in six cases of neuroblastoma. The supernumerary gene copies are commonly found on highly rearranged, extrachromosomal circular DNA (ecDNA). The exact amplicon structure has not been described thus far and the functional relevance of its rearrangements is unknown. Here, we analyze the MYCN amplicon structure using short-read and Nanopore sequencing and its chromatin landscape using ChIP-seq, ATAC-seq and Hi-C. This reveals two distinct classes of amplicons which explain the regulatory requirements for MYCN overexpression. The first class always co-amplifies a proximal enhancer driven by the noradrenergic core regulatory circuit (CRC). The second class of MYCN amplicons is characterized by high structural complexity, lacks key local enhancers, and instead contains distal chromosomal fragments harboring CRC-driven enhancers. Thus, ectopic enhancer hijacking can compensate for the loss of local gene regulatory elements and explains a large component of the structural diversity observed in MYCN amplification.

Details

show
hide
Language(s): eng - English
 Dates: 2020-09-302020-11-16
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1038/s41467-020-19452-y
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 2020 (11) Sequence Number: 11:5823 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723