| Status | 已發表Published |
| Global Analysis of CreA Regulatory Network in Aspergillus nidulans | |
Chen, Y.; Dong, L. ; Alam, M. A.; Wang, F.; Kelly, J.; Wong, K. H. 
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| 2017-03-14 | |
| Source Publication | 29th Fungal Genetics Conference
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| Abstract | Carbon metabolism is central to all living organisms governing many physiological processes including cell growth and development. In Aspergillus nidulans, carbon metabolism is tightly controlled at the transcription level by a process known as carbon catabolite repression (CCR). CCR is mediated by a global transcriptional repressor called CreA. Despite decades of research on CreA, the full spectrum of CreA targets and how it globally regulates and coordinate expression of genes involved in different carbon metabolic pathways remain unclear. In an attempt to address these questions, we applied and integrated two powerful approaches RNA-seq and ChIP-seq for a genome-wide study of CreA under repressing and derepressing conditions. We discovered that CreA binds to several thousands promoters in the genome. The bindings are found mainly at the nucleosome-depleted promoter regions and are enriched with GC-rich motifs along with many other motifs, which are likely the recognition sequences of partner regulators. The set of CreA direct targets include genes involved in biosynthetic process, transmembrane transport, response to stimulus, regulation of transcription, ion homeostasis and sexual reproduction. Some of these roles have been confirmed by functional tests. Interestingly, our analysis reveals that the CreA binding intensity, the number of CreA binding sites and additional motifs are associated with different sets of CreA target genes of different physiological functions. Moreover, our genome-wide ChIPseq data also revealed that CreA constitutively binds to the target promoters at similar levels under both repression and de-repression conditions, even for genes whose expression is markedly increased (i.e. de-repressed) under the de-repression condition. This observation strongly indicates that CreA binding alone is not sufficient for CreA regulation, and in turn suggests that the nuclear CreA levels under these conditions are not the determining factor for CreA repression or de-repression. Rather, this finding implies that post-translational modification(s) play(s) crucial role in CreA regulation. Transcription profiling analysis by RNAseq of wildtype and creA∆ mutant strains reveals that CreA not only acts as a transcription repressor, but also has a positive role for many target genes. Surprisingly, we found that expression of more than half of CreA bound genes are not significantly affected in the creA∆ strain. This suggests that either CreA pauses at many promoters pending modification for function or the activators responsible for activating those genes are not available for function under our experimental conditions. Taken together, our results reveal a comprehensive global CreA regulatory network at a whole-genome level and illuminate novel CreA regulating patterns and functions. |
| Keyword | CreA Aspergillus carbon |
| Language | 英語English |
| The Source to Article | PB_Publication |
| PUB ID | 32159 |
| Document Type | Conference paper |
| Collection | DEPARTMENT OF BIOMEDICAL SCIENCES Faculty of Health Sciences |
| Corresponding Author | Wong, K. H. |
| Recommended Citation GB/T 7714 | Chen, Y.,Dong, L.,Alam, M. A.,et al. Global Analysis of CreA Regulatory Network in Aspergillus nidulans[C], 2017. |
| APA | Chen, Y.., Dong, L.., Alam, M. A.., Wang, F.., Kelly, J.., & Wong, K. H. (2017). Global Analysis of CreA Regulatory Network in Aspergillus nidulans. 29th Fungal Genetics Conference. |
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