| Epigenetic controlling and chromatin remodelling are involved in embryonic development and cancer. Histone acetylation is one of the key modifications to control gene transcription during embryonic genesis and tumorigenesis. Histone deacetylases (HDACs) catalyze the removal of acetyl groups from core histones, resulting in changes of chromatin structure and gene transcription activity. Recent years, the accumulating knowledge of the role of HDACs in tumorigenesis, and of the action of HDAC inhibitors, has been achieved. HDACs inhibitor are considered to be among the most promising targets in drug development for cancer therapy. However, the basic aspects of what kinds of genes are more sensitive to exposure of histone deacetylase inhibitor in vivo are not yet fully understood. The limb genesis is an excellent model for studying gene expression and regulation, as a batch of limb development related gene, gene expression patterns and function has been identified. Taking chicken embryonic limb as an experimental model, we have investigated the reaction of a batch of genes in the limbs treated with Trichostatin A (TSA), a histone deacetylase (HDAC)-inhibitor. The results show that TSA (75μM) changes the expression levels of the genes, which have important functions during limb development. Among then, BMP4, SF/HGF and Twist1 were up-regulated;BMP2, FGF8, Shh, Scleraxis, Myf5 and MyoD were down-regulated. In contrast to that, the Pax3, Paraxis, Msx1, CREB, and PCNA were still expressed at the same levels as controls. Increasing the concentration of TSA (>750 μM) can induce apoptosis and embryonic limb malformations. Our results indicate that chicken limb development can serve as a convenient in vivo model for studying the effect of HDAC inhibitors on gene expression. It may be useful for improving our understanding of the role of chromatin remodelling and epigenetic control of gene expression patterns and developing the drugs against cancer. |
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