Skip to main content

Research Repository

See what's under the surface

Advanced Search

Acetylation of TBX5 by KAT2B and KAT2A regulates heart and limb development

Ghosh, Tushar K.; Aparicio-Sánchez, José J.; Buxton, Sarah; Ketley, Ami; Mohamed, Tasabeeh; Rutland, Catrin S.; Loughna, Siobhan; Brook, J. David

Authors

Tushar K. Ghosh

José J. Aparicio-Sánchez

Sarah Buxton

Ami Ketley

Tasabeeh Mohamed

Catrin S. Rutland

Siobhan Loughna

J. David Brook david.brook@nottingham.ac.uk



Abstract

TBX5 plays a critical role in heart and forelimb development. Mutations in TBX5 cause Holt-Oram syndrome, an autosomal dominant condition that affects the formation of the heart and upper - limb. Several studies have provided significant insight into the role of TBX5 in cardiogenesis; however, how TBX5 activity is regulated by other factors is still unknown. Here we report that histone acetyltransferases KAT2A and KAT2B associate with TBX5 and acetylateit at Lys339. Acetylation potentiates its transcriptional activity and is required for nuclear retention. Morpholino-mediated knockdown of kat2a and kat2b transcripts in zebrafish severely perturb heart and limb development, mirroring the tbx5a knockdown phenotype. The phenotypes found in MO-injected embryos were also observed when we introduced mutations in the kat2a or kat2b genes using the CRISPR-Cas system. The sestudies highlight the importance of KAT2A and KAT2B modulation of TBX5 and their impact on heart and limb development

Journal Article Type Article
Publication Date Jan 31, 2018
Journal Journal of Molecular and Cellular Cardiology
Print ISSN 0022-2828
Electronic ISSN 1095-8584
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 114
APA6 Citation Ghosh, T. K., Aparicio-Sánchez, J. J., Buxton, S., Ketley, A., Mohamed, T., Rutland, C. S., …Brook, J. D. (2018). Acetylation of TBX5 by KAT2B and KAT2A regulates heart and limb development. Journal of Molecular and Cellular Cardiology, 114, doi:10.1016/j.yjmcc.2017.11.013
DOI https://doi.org/10.1016/j.yjmcc.2017.11.013
Keywords TBX5, acetylation, heart development, CRISPR-Cas, zebrafish
Publisher URL http://www.sciencedirect.com/science/article/pii/S0022282817303486?via%3Dihub
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0

Files

Acetylation of TBX5 by KAT2B and KAT2A regulates heart and limb development.pdf (9.1 Mb)
PDF

Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0


TBX5 acetylation paper - Supplementary figures1.pdf (932 Kb)
PDF

Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0


TBX5 acetylation paper - Supplementary figures legends (Publication)1.pdf (1.2 Mb)
PDF

Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0





You might also like



Downloadable Citations

;