Acetylation of TBX5 by KAT2B and KAT2A regulates heart and limb development
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...
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| Format: | Article |
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Elsevier
2018
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| Online Access: | https://eprints.nottingham.ac.uk/48810/ |
| _version_ | 1848797853343809536 |
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| author | Ghosh, Tushar K. Aparicio-Sánchez, José J. Buxton, Sarah Ketley, Ami Mohamed, Tasabeeh Rutland, Catrin S. Loughna, Siobhan Brook, J. David |
| author_facet | Ghosh, Tushar K. Aparicio-Sánchez, José J. Buxton, Sarah Ketley, Ami Mohamed, Tasabeeh Rutland, Catrin S. Loughna, Siobhan Brook, J. David |
| author_sort | Ghosh, Tushar K. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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 |
| first_indexed | 2025-11-14T20:10:28Z |
| format | Article |
| id | nottingham-48810 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:10:28Z |
| publishDate | 2018 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-488102020-05-04T19:29:03Z https://eprints.nottingham.ac.uk/48810/ 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 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 Elsevier 2018-01-31 Article PeerReviewed Ghosh, Tushar K., Aparicio-Sánchez, José J., Buxton, Sarah, Ketley, Ami, Mohamed, Tasabeeh, Rutland, Catrin S., Loughna, Siobhan and Brook, J. David (2018) Acetylation of TBX5 by KAT2B and KAT2A regulates heart and limb development. Journal of Molecular and Cellular Cardiology, 114 . pp. 185-198. ISSN 1095-8584 TBX5 acetylation heart development CRISPR-Cas zebrafish http://www.sciencedirect.com/science/article/pii/S0022282817303486?via%3Dihub doi:10.1016/j.yjmcc.2017.11.013 doi:10.1016/j.yjmcc.2017.11.013 |
| spellingShingle | TBX5 acetylation heart development CRISPR-Cas zebrafish Ghosh, Tushar K. Aparicio-Sánchez, José J. Buxton, Sarah Ketley, Ami Mohamed, Tasabeeh Rutland, Catrin S. Loughna, Siobhan Brook, J. David Acetylation of TBX5 by KAT2B and KAT2A regulates heart and limb development |
| title | Acetylation of TBX5 by KAT2B and KAT2A regulates heart and limb development |
| title_full | Acetylation of TBX5 by KAT2B and KAT2A regulates heart and limb development |
| title_fullStr | Acetylation of TBX5 by KAT2B and KAT2A regulates heart and limb development |
| title_full_unstemmed | Acetylation of TBX5 by KAT2B and KAT2A regulates heart and limb development |
| title_short | Acetylation of TBX5 by KAT2B and KAT2A regulates heart and limb development |
| title_sort | acetylation of tbx5 by kat2b and kat2a regulates heart and limb development |
| topic | TBX5 acetylation heart development CRISPR-Cas zebrafish |
| url | https://eprints.nottingham.ac.uk/48810/ https://eprints.nottingham.ac.uk/48810/ https://eprints.nottingham.ac.uk/48810/ |