Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom.
Mol Cell Biol. 2010 Jul;30(13):3396-410. doi: 10.1128/MCB.00971-09. Epub 2010 Apr 19.
Expression of nitrogen metabolism genes is regulated by the quality of the nitrogen supply. Here, we describe a mechanism for the transcriptional regulation of the general amino acid permease gene per1 in Schizosaccharomyces pombe. We show that when ammonia is used as the nitrogen source, low levels of per1 are transcribed and histones in the coding and surrounding regions of per1 are acetylated. In the presence of proline, per1 transcription is upregulated and initiates from a more upstream site, generating 5'-extended mRNAs. Concomitantly, histones at per1 are deacetylated in a Clr6-dependent manner, suggesting a positive role for Clr6 in transcriptional regulation of per1. Upstream initiation and histone deactylation of per1 are constitutive in cells lacking the serine/threonine kinase oca2, indicating that Oca2 is a repressor of per1. Oca2 interacts with a protein homologous to the Saccharomyces cerevisiae transcriptional activator Cha4 and with Ago1. Loss of Cha4 or Ago1 causes aberrant induction of per1 under noninducing conditions, suggesting that these proteins are also involved in per1 regulation and hence in nitrogen utilization.
氮代谢基因的表达受氮源质量的调控。在这里，我们描述了一种真菌 Schizosaccharomyces pombe 中普遍氨基酸渗透酶基因 per1 转录调控的机制。我们发现，当氨作为氮源时，per1 的转录水平较低，per1 编码区和周围区域的组蛋白发生乙酰化。在脯氨酸存在的情况下，per1 的转录被上调，并从更上游的位点起始，产生 5'延伸的 mRNA。同时，per1 处的组蛋白以 Clr6 依赖性方式去乙酰化，表明 Clr6 在 per1 的转录调控中起正向作用。在缺乏丝氨酸/苏氨酸激酶 oca2 的细胞中，per1 的上游起始和组蛋白去乙酰化是组成性的，表明 Oca2 是 per1 的阻遏物。Oca2 与酿酒酵母转录激活因子 Cha4 和 Ago1 的同源蛋白相互作用。Cha4 或 Ago1 的缺失导致 per1 在非诱导条件下异常诱导，表明这些蛋白也参与 per1 的调控，进而参与氮的利用。
