Rao Jyothsna, Bhattacharya Dipanjan, Banerjee Bidisha, Sarin Apurva, Shivashankar G V
SASTRA University, Tanjore 613402, India.
Biochem Biophys Res Commun. 2007 Nov 16;363(2):263-8. doi: 10.1016/j.bbrc.2007.08.120. Epub 2007 Aug 29.
Trichostatin-A (TSA), a histone deacetylase (HDAC) inhibitor, results in enhanced acetylation of core histones thereby disrupting chromatin organization within living cells. We report on changes in chromatin organization and the resultant alteration in nuclear architecture following treatment with TSA using fluorescence imaging. TSA triggers an expected increase in the euchromatin fraction which is accompanied by a significant increase in nuclear volume and alterations in chromatin compaction mapped using fluorescence anisotropy imaging. We observe differential changes in the mobility of core and linker histones as measured by fluorescence recovery after photo-bleaching (FRAP) and fluorescence correlation spectroscopy (FCS) methods. Further TSA induces a differential increase in linker histone transcription and increased phosphorylation of linker histone proteins accompanying an expected increase in core histone acetylation patterns. Thus subtle feedback responses triggered by changes in chromatin configurations impinge selectively on linker histone mobility and its expression. These observations have implications for understanding the role of HDAC in the dynamic maintenance of chromatin organization.
曲古抑菌素A（TSA）是一种组蛋白去乙酰化酶（HDAC）抑制剂，可导致核心组蛋白乙酰化增强，从而破坏活细胞内的染色质组织。我们使用荧光成像技术报告了用TSA处理后染色质组织的变化以及由此导致的核结构改变。TSA引发常染色质部分的预期增加，同时核体积显著增加，并且使用荧光各向异性成像绘制了染色质压缩的变化。我们观察到通过光漂白后荧光恢复（FRAP）和荧光相关光谱（FCS）方法测量的核心组蛋白和连接组蛋白迁移率的差异变化。此外，TSA诱导连接组蛋白转录的差异增加以及连接组蛋白蛋白磷酸化增加，同时核心组蛋白乙酰化模式预期增加。因此，染色质构型变化引发的微妙反馈反应选择性地影响连接组蛋白的迁移率及其表达。这些观察结果对于理解HDAC在染色质组织动态维持中的作用具有重要意义。
