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

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.
Authors	Tushar K Ghosh, José J Aparicio-Sánchez, Sarah Buxton, J David Brook
Journal	Scientific reports (Sci Rep) Vol. 9 Issue 1 Pg. 17992 (11 29 2019) ISSN: 2045-2322 [Electronic] England
PMID	31784580 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	MEF2 Transcription Factors MEF2C protein, human Recombinant Proteins Repressor Proteins T-Box Domain Proteins T-box transcription factor 5 protein kinase D Protein Kinase C HDAC4 protein, human HDAC5 protein, human Histone Deacetylases
Topics	Abnormalities, Multiple (genetics, pathology) Acetylation Animals COS Cells Chlorocebus aethiops Cloning, Molecular Cytoplasm (metabolism) Heart Defects, Congenital (genetics, pathology) Heart Septal Defects, Atrial (genetics, pathology) Histone Deacetylases (metabolism) Lower Extremity Deformities, Congenital (genetics, pathology) MEF2 Transcription Factors (metabolism) Protein Kinase C (genetics, isolation & purification, metabolism) Rats Recombinant Proteins (genetics, isolation & purification, metabolism) Repressor Proteins (metabolism) T-Box Domain Proteins (genetics, metabolism) Transcription, Genetic Transfection Upper Extremity Deformities, Congenital (genetics, pathology)

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