kth.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
CBP-HSF2 structural and functional interplay in Rubinstein-Taybi neurodevelopmental disorder
Univ Paris, CNRS, Epigenet & Cell Fate, F-75013 Paris, France..ORCID iD: 0000-0003-0405-0745
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. Abo Akad Univ, Fac Sci & Engn, Cell Biol, Turku, Finland.;Univ Turku, Turku Biosci Ctr, Turku, Finland..ORCID iD: 0000-0001-6256-4694
Univ Paris, CNRS, Epigenet & Cell Fate, F-75013 Paris, France..
Number of Authors: 382022 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 13, no 1, article id 7002Article in journal (Refereed) Published
Abstract [en]

Rubinstein-Taybi syndrome (RSTS) is a neurodevelopmental disorder with unclear underlying mechanisms. Here, the authors unravel the contribution of a stress-responsive pathway to RSTS where impaired HSF2 acetylation, due to RSTS-associated CBP/EP300 mutations, alters the expression of neurodevelopmental players, in keeping with hallmarks of cell-cell adhesion defects. Patients carrying autosomal dominant mutations in the histone/lysine acetyl transferases CBP or EP300 develop a neurodevelopmental disorder: Rubinstein-Taybi syndrome (RSTS). The biological pathways underlying these neurodevelopmental defects remain elusive. Here, we unravel the contribution of a stress-responsive pathway to RSTS. We characterize the structural and functional interaction between CBP/EP300 and heat-shock factor 2 (HSF2), a tuner of brain cortical development and major player in prenatal stress responses in the neocortex: CBP/EP300 acetylates HSF2, leading to the stabilization of the HSF2 protein. Consequently, RSTS patient-derived primary cells show decreased levels of HSF2 and HSF2-dependent alteration in their repertoire of molecular chaperones and stress response. Moreover, we unravel a CBP/EP300-HSF2-N-cadherin cascade that is also active in neurodevelopmental contexts, and show that its deregulation disturbs neuroepithelial integrity in 2D and 3D organoid models of cerebral development, generated from RSTS patient-derived iPSC cells, providing a molecular reading key for this complex pathology.

Place, publisher, year, edition, pages
Springer Nature , 2022. Vol. 13, no 1, article id 7002
National Category
Medical Genetics Neurology
Identifiers
URN: urn:nbn:se:kth:diva-322356DOI: 10.1038/s41467-022-34476-2ISI: 000884843700017PubMedID: 36385105Scopus ID: 2-s2.0-85142166002OAI: oai:DiVA.org:kth-322356DiVA, id: diva2:1718044
Note

Correction in Nature Communications, vol. 14, issue. 1. DOI:10.1038/s41467-023-41869-4

QC 20231030

Available from: 2022-12-12 Created: 2022-12-12 Last updated: 2023-10-30Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMedScopus

Authority records

Vihervaara, Anniina

Search in DiVA

By author/editor
de Thonel, AurelieVihervaara, Anniina
By organisation
Gene Technology
In the same journal
Nature Communications
Medical GeneticsNeurology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 25 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf