Moreira J M, Holmberg S
Department of Genetics, Institute of Molecular Biology, University of Copenhagen, Oster Farimagsgade 2A, DK-1353 Copenhagen K, Denmark.
EMBO J. 2000 Dec 15;19(24):6804-13. doi: 10.1093/emboj/19.24.6804.
The Saccharomyces cerevisiae NHP6A and NHP6B proteins are chromatin architectural factors, functionally and structurally related to the mammalian high mobility group (HMG)-1 and -2 proteins, a family of non-sequence-specific DNA binding proteins. nhp6a nhp6b mutants have various morphological defects and are defective in the induced expression of several RNA polymerase II-transcribed genes. We found that NHP6A/B proteins are also required for full induction of the yeast CHA1 gene. Importantly, CHA1 basal level expression is increased 10-fold in an nhp6a nhp6b double deletion mutant. Micrococcal nuclease and DNase I analysis of the CHA1 gene in this strain showed an open promoter structure, characteristic of the activated state of this promoter, even under non-inducing conditions. To address the possible function of the NHP6A/B proteins in chromatin-mediated gene regulation, we performed whole-genome transcriptional profiling of a Deltanhp6a Deltanhp6b yeast strain. Our results suggest that NHP6A/B proteins play an important regulatory role, repressing as well as potentiating expression of genes involved in several cellular processes, and that NHP6A/B control is exerted at the level of the individual gene.
酿酒酵母的NHP6A和NHP6B蛋白是染色质结构因子,在功能和结构上与哺乳动物高迁移率族(HMG)-1和-2蛋白相关,后者是一类非序列特异性DNA结合蛋白家族。nhp6a nhp6b突变体具有多种形态缺陷,并且在几种RNA聚合酶II转录基因的诱导表达方面存在缺陷。我们发现NHP6A/B蛋白对于酵母CHA1基因的完全诱导也是必需的。重要的是,在nhp6a nhp6b双缺失突变体中,CHA1的基础水平表达增加了10倍。对该菌株中CHA1基因进行的微球菌核酸酶和DNase I分析表明,即使在非诱导条件下,该启动子也呈现开放的启动子结构,这是该启动子激活状态的特征。为了研究NHP6A/B蛋白在染色质介导的基因调控中的可能功能,我们对Δnhp6a Δnhp6b酵母菌株进行了全基因组转录谱分析。我们的结果表明,NHP6A/B蛋白发挥重要的调节作用,既能抑制也能增强参与多个细胞过程的基因的表达,并且NHP6A/B的调控作用是在单个基因水平上发挥的。