Lucau-Danila Ancuta, Delaveau Thierry, Lelandais Gaëlle, Devaux Frédéric, Jacq Claude
Laboratoire de Génétique Moléculaire, Ecole Normale Supérieure, 46 rue d'Ulm 75230 Paris cedex 05, France.
J Biol Chem. 2003 Dec 26;278(52):52641-50. doi: 10.1074/jbc.M309580200. Epub 2003 Sep 25.
Highly flexible gene expression programs are required to allow cell growth in the presence of a wide variety of chemicals. We used genome-wide expression analyses coupled with chromatin immunoprecipitation experiments to study the regulatory relationships between two very similar yeast transcription factors involved in the control of the multidrug resistance phenomenon. Yrm1 (Yor172w) is a new zinc finger transcription factor, the overproduction of which decreases the level of transcription of the target genes of Yrr1, a zinc finger transcription factor controlling the expression of several membrane transporter-encoding genes. Surprisingly, the absence of YRR1 releases the transcriptional activity of Yrm1, which then up-regulates 23 genes, 14 of which are also direct target genes of Yrr1. Chromatin immunoprecipitation experiments confirmed that Yrm1 binds to the promoters of the up-regulated genes only in yeast strains from which YRR1 has been deleted. This sophisticated regulatory program can be associated with drug resistance phenotypes of the cell. The program-specific distribution of paired transcription factors throughout the genome may be a general mechanism by which similar transcription factors regulate overlapping gene expression programs in response to chemical stress.
高度灵活的基因表达程序对于细胞在多种化学物质存在的情况下生长是必需的。我们使用全基因组表达分析结合染色质免疫沉淀实验来研究两个参与多药耐药现象控制的非常相似的酵母转录因子之间的调控关系。Yrm1（Yor172w）是一种新的锌指转录因子，其过量表达会降低Yrr1靶基因的转录水平，Yrr1是一种控制多个膜转运蛋白编码基因表达的锌指转录因子。令人惊讶的是，YRR1的缺失释放了Yrm1的转录活性，然后Yrm1上调了23个基因，其中14个也是Yrr1的直接靶基因。染色质免疫沉淀实验证实，Yrm1仅在缺失YRR1的酵母菌株中与上调基因的启动子结合。这种复杂的调控程序可能与细胞的耐药表型有关。成对转录因子在全基因组中的程序特异性分布可能是一种普遍机制，通过该机制相似的转录因子响应化学应激调节重叠基因表达程序。
