School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK.
Sci Rep. 2019 Nov 29;9(1):17992. doi: 10.1038/s41598-019-54312-w.
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.
TBX5 是 T 盒家族转录因子，在脊椎动物中调节心脏和前肢发育，该蛋白的功能缺失会导致 Holt-Oram 综合征。最近，我们已经证明 TBX5 的乙酰化可以增强其活性，对心脏和肢体发育很重要。在这里，我们报告说，II 类组蛋白去乙酰化酶 HDAC4 和 HDAC5 与 TBX5 结合，并抑制其在心脏基因转录中的作用。HDAC4 和 HDAC5 都使 TBX5 去乙酰化，这促进了 TBX5 向细胞质的重新定位，HDAC4 拮抗 TBX5 与 MEF2C 之间的物理关联和功能合作。我们还表明，蛋白激酶 D1（PRKD1）缓解了 HDAC4/5 对 TBX5 的抑制作用。因此，本研究揭示了 HDAC4/5 和 PRKD1 在调节 TBX5 转录活性中的新相互作用。
