Communication between levels of transcriptional control improves robustness and adaptivity

• Published in: Molecular systems biology 2006, Vol.2 (1), p.65-n/a
• Main Authors: Silver, Pamela A, Tsankov, Alexander M, Brown, Christopher R, Yu, Michael C, Win, Moe Z, Casolari, Jason M
• Format: Article
• Language: English
• Subjects: Algorithms; Binding sites; Chromatin; Communication; Communication theory; Deoxyribonucleic acid; DNA; EMBO09; EMBO30; Experiments; Functional groups; Gene expression; Gene Expression Regulation, Fungal; Gene Regulatory Networks; Genomes; Histone Deacetylases - metabolism; Methods; Nuclear Proteins - metabolism; Nuclear transport; Protein Binding; Proteins; Regulators; Reproducibility of Results; RNA processing; RNA transport; Robust control; Robustness; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins - metabolism; Silent Information Regulator Proteins, Saccharomyces cerevisiae - metabolism; Sirtuin 2; Sirtuins - metabolism; Transcription initiation; Transcription, Genetic
• ISSN: 1744-4292; 1744-4292
• DOI: 10.1038/msb4100106

Regulation of eukaryotic gene expression depends on groups of related proteins acting at the levels of chromatin organization, transcriptional initiation, RNA processing, and nuclear transport. However, a unified understanding of how these different levels of transcriptional control interact has been lacking. Here, we combine genome‐wide protein–DNA binding data from multiple sources to infer the connections between functional groups of regulators in Saccharomyces cerevisiae . Our resulting transcriptional network uncovers novel biological relationships; supporting experiments confirm new associations between actively transcribed genes and Sir2 and Esc1, two proteins normally linked to silencing chromatin. Analysis of the regulatory network also reveals an elegant architecture for transcriptional control. Using communication theory, we show that most protein regulators prefer to form modules within their functional class, whereas essential proteins maintain the sparse connections between different classes. Moreover, we provide evidence that communication between different regulatory groups improves the robustness and adaptivity of the cell. Synopsis The nucleus is the distinguishing feature of the eukaryotic cell. It provides added mechanisms for regulating gene expression at the levels of chromatin organization, RNA processing, and selective export via the nuclear pore complex. Groups of proteins that mediate these processes have been extensively characterized. We propose that these functional groups of proteins exhibit extensive connectivity within and between groups in order to establish and maintain the transcriptional and nuclear architecture. These groups include transcription factors (TFs), RNA processing and nuclear proteins (RPs), nuclear transport (import/export) proteins (NTs), nucleosome remodelers (NRs), histone modification (e.g. acetylation) states (HSs), and histone modifying proteins (HMs). Chromatin‐immunoprecipitation experiments in combination with microarrays (termed ChIP‐chip) have mapped the genomic occupancy of the aforementioned protein classes in living cells. Genome‐wide identification of binding sites has allowed for the inference of which genes are regulated by such factors. For example, various TFs, HMs, and NRs have been shown to regulate specific gene expression programs (Lee et al , 2002 ; Ng et al , 2002 ; Robyr et al , 2002 ; Bar‐Joseph et al , 2003 ; Robert et al , 2004 ; Gelbart et al , 2005 ). However, a unified model