HDAC4 and 5 repression of TBX5 is relieved by protein kinase D1

Ghosh, Tushar K.; Aparicio-S�nchez, Jos� J.; Buxton, Sarah; Brook, J. David

Abstract

TBX5 is a T-box family transcription factor that regulates heart and forelimb development in vertebrates and functional deficiencies in this protein result in Holt-Oram syndrome. Recently, we have shown that acetylation of TBX5 potentiates its activity and is important for heart and limb development. Here we report that class II histone deacetylases HDAC4 and HDAC5 associate with TBX5 and repress its role in cardiac gene transcription. Both HDAC4 and HDAC5 deacetylate TBX5, which promotes its relocation to the cytoplasm and HDAC4 antagonizes the physical association and functional cooperation between TBX5 and MEF2C. We also show that protein kinase D1 (PRKD1) relieves the HDAC4/5-mediated repression of TBX5. Thus, this study reveals a novel interaction of HDAC4/5 and PRKD1 in the regulation of TBX5 transcriptional activity.

Citation

Ghosh, T. K., Aparicio-Sánchez, J. J., Buxton, S., & Brook, J. D. (2019). HDAC4 and 5 repression of TBX5 is relieved by protein kinase D1. Scientific Reports, 9, Article 17992. https://doi.org/10.1038/s41598-019-54312-w

• Journal Article Type: Article
• Acceptance Date: Sep 11, 2019
• Online Publication Date: Nov 29, 2019
• Publication Date: 2019-12
• Deposit Date: Dec 3, 2019
• Publicly Available Date: Dec 3, 2019
• Journal: Scientific Reports
• Electronic ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Article Number: 17992
• DOI: https://doi.org/10.1038/s41598-019-54312-w
• Public URL: https://nottingham-repository.worktribe.com/output/3465328
• Publisher URL: https://www.nature.com/articles/s41598-019-54312-w
• Additional Information: Received: 5 April 2019; Accepted: 11 September 2019; First Online: 29 November 2019; : The authors declare no competing interests.