Neuronal genes deregulated in Cornelia de Lange Syndrome respond to removal and re-expression of cohesin

Felix D. Weiss, Lesly Calderon, Yi-Fang Wang, Radina Georgieva, Ya Guo, Nevena Cvetesic, Maninder Kaur, Gopuraja Dharmalingam, Ian D. Krantz, Boris Lenhard, Amanda G. Fisher and Matthias Merkenschlager ()
Additional contact information
Felix D. Weiss: Imperial College London
Lesly Calderon: Imperial College London
Yi-Fang Wang: Imperial College London
Radina Georgieva: Imperial College London
Ya Guo: Imperial College London
Nevena Cvetesic: Imperial College London
Maninder Kaur: The Children’s Hospital of Philadelphia
Gopuraja Dharmalingam: Imperial College London
Ian D. Krantz: The Children’s Hospital of Philadelphia
Boris Lenhard: Imperial College London
Amanda G. Fisher: Imperial College London
Matthias Merkenschlager: Imperial College London

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Cornelia de Lange Syndrome (CdLS) is a human developmental disorder caused by mutations that compromise the function of cohesin, a major regulator of 3D genome organization. Cognitive impairment is a universal and as yet unexplained feature of CdLS. We characterize the transcriptional profile of cortical neurons from CdLS patients and find deregulation of hundreds of genes enriched for neuronal functions related to synaptic transmission, signalling processes, learning and behaviour. Inducible proteolytic cleavage of cohesin disrupts 3D genome organization and transcriptional control in post-mitotic cortical mouse neurons, demonstrating that cohesin is continuously required for neuronal gene expression. The genes affected by acute depletion of cohesin belong to similar gene ontology classes and show significant numerical overlap with genes deregulated in CdLS. Interestingly, reconstitution of cohesin function largely rescues altered gene expression, including the expression of genes deregulated in CdLS.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-23141-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23141-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-23141-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().