Mehrotra Swati, Galdieri Luciano, Zhang Tiantian, Zhang Man, Pemberton Lucy F, Vancura Ales
Department of Biological Sciences, St. John's University, Queens, NY 11439, USA.
Center for Cell Signalling, Department of Microbiology, University of Virginia Health Sciences Center, University of Virginia, Charlottesville, VA 22908, USA.
Biochim Biophys Acta. 2014 Sep;1839(9):751-63. doi: 10.1016/j.bbagrm.2014.05.029. Epub 2014 Jun 5.
Transcriptional activation is typically associated with increased acetylation of promoter histones. However, this paradigm does not apply to transcriptional activation of all genes. In this study we have characterized a group of genes that are repressed by histone acetylation. These histone hypoacetylation-activated genes (HHAAG) are normally repressed during exponential growth, when the cellular level of acetyl-CoA is high and global histone acetylation is also high. The HHAAG are induced during diauxic shift, when the levels of acetyl-CoA and global histone acetylation decrease. The histone hypoacetylation-induced activation of HHAAG is independent of Msn2/Msn4. The repression of HSP12, one of the HHAAG, is associated with well-defined nucleosomal structure in the promoter region, while histone hypoacetylation-induced activation correlates with delocalization of positioned nucleosomes or with reduced nucleosome occupancy. Correspondingly, unlike the majority of yeast genes, HHAAG are transcriptionally upregulated when expression of histone genes is reduced. Taken together, these results suggest a model in which histone acetylation is required for proper positioning of promoter nucleosomes and repression of HHAAG.
转录激活通常与启动子组蛋白的乙酰化增加有关。然而，这种模式并不适用于所有基因的转录激活。在本研究中，我们鉴定了一组受组蛋白乙酰化抑制的基因。这些组蛋白低乙酰化激活基因（HHAAG）在指数生长期通常受到抑制，此时细胞内乙酰辅酶A水平较高且整体组蛋白乙酰化水平也较高。HHAAG在二次生长转换期间被诱导，此时乙酰辅酶A水平和整体组蛋白乙酰化水平降低。组蛋白低乙酰化诱导的HHAAG激活不依赖于Msn2/Msn4。HHAAG之一的HSP12的抑制与启动子区域明确的核小体结构相关，而组蛋白低乙酰化诱导的激活与定位核小体的离域或核小体占有率降低相关。相应地，与大多数酵母基因不同，当组蛋白基因的表达降低时，HHAAG的转录会上调。综上所述，这些结果提示了一种模型，其中组蛋白乙酰化对于启动子核小体的正确定位和HHAAG的抑制是必需的。
