Hierarchical organization of the network of genes controlled by the circadian clock of Neurospora

生物钟以一天中特定时间的方式协调大型基因网络的表达，因此对于维持细胞内稳态至关重要。白色项圈复合体（White Collar Complex，WCC）是脉孢菌生物钟的核心转录调节因子。它可以直接或间接调节1000多个时钟控制基因的表达。这些基因中的绝大多数是未知的。我们的目标是确定WCC激活基因的WCC结合位点的全基因组分析。使用ChIP结合高通量测序，我们已经确定了超过250个可能的WCC直接靶基因。通过各种独立的方法验证所选候选基因，包括ChIP RT-PCR和报告基因测定。此外，将表征基因产物并分析相应敲除菌株的表型。为了解开时钟控制基因的层次网络，WCC依赖性基因编码转录调节因子的分析和其靶基因的全基因组分析是特别感兴趣的。

Circadian clocks coordinate expression of large networks of genes in a timeof- day specific manner and are thus crucial for the maintenance of cellular homeostasis. The White Collar Complex (WCC) is the central transcription regulator of the circadian clock of Neurospora. It may directly or indirectly modulate expression of more than 1000 clock-controlled genes. The vast majority of these genes are not known. We aim to identify WCC-activated genes by a genome-wide analysis of WCC binding sites. Using ChIP in combination with high-throughput sequencing we have identified more than 250 likely direct target genes of the WCC. Selected candidate genes are validated by various independent methods, including ChIP RT-PCR and reporter assays. Furthermore, gene products will be characterized and phenotypes of corresponding knockout strains will be analyzed. To unravel the hierarchical network of clock-controlled genes the analysis of WCCdependent genes encoding transcriptional regulators and genome wide analysis of their target genes are of particular interest.