Identification of HDAC regulating hGCMa activity

• Main Authors: Hsiao-Ching Chuang, 莊筱菁
• Other Authors: Hung-Wen Chen
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/57566863269535466720

碩士 === 國立臺灣大學 === 生化科學研究所 === 93 === Human GCMa is a zinc-containing transcription factor that plays a critical role for placenta development. hGCMa regulates the fusion of cytotrophoblasts into a syncytiotrophoblast layer, which is indispensable for the proper development of fetus. In our previous studies, we have demonstrated that PKA stimulates the association of hGCMa with CBP and increases hGCMa acetylation by CBP. Because hGCMa acetylation enhances its stability and transcriptional activity, there should be a negative regulation system, such as a deacetylation mechanism, to reverse hGCMa activity. In the current study, we observed that trichostatin A (TSA), an inhibitor of multiple histone deacetylases (HDACs), enhances the acetylation state of hGCMa and hGCMa-mediated transcriptional activity. We further found that hGCMa can be deacetylated through the interaction with HDACα, HDACγ, HDACκ and HDACλ Because HDACγ displayed the strongest deacetylation effect and binding efficiency, we also demonstrated that HDACγinhibits hGCMa-mediated transcriptional activity in transient expression experiments. These results suggest that acetylated hGCMa is a substrate for several deacetylases and reveal a new mechanism for the posttranslational regulation of hGCMa activity by histone acetyl-transferase and deacetylases.