Dynamic Changes in Subgraph Preference Profiles of Crucial Transcription Factors

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Abstract
Transcription factors with a large number of target genes—transcription hub(s), or THub(s)—are usually crucial components of the regulatory system of a cell, and the different patterns through which they transfer the transcriptional signal to downstream cascades are of great interest. By profiling normalized abundances (AN) of basic regulatory patterns of individual THubs in the yeast Saccharomyces cerevisiae transcriptional regulation network under five different cellular states and environmental conditions, we have investigated their preferences for different basic regulatory patterns. Subgraph-normalized abundances downstream of individual THubs often differ significantly from that of the network as a whole, and conversely, certain over-represented subgraphs are not preferred by any THub. The THub preferences changed substantially when the cellular or environmental conditions changed. This switching of regulatory pattern preferences suggests that a change in conditions does not only elicit a change in response by the regulatory network, but also a change in the mechanisms by which the response is mediated. The THub subgraph preference profile thus provides a novel tool for description of the structure and organization between the large-scale exponents and local regulatory patterns. Transcription factors are proteins that bind to short segments of DNA, thereby controlling transcription and expression of other genes. Transcription factors may control a number of other genes, and in turn be controlled by other transcription factors, thus forming an extensive transcriptional network of control and counter-control, which acts through space and time in the cell. In transcriptional networks, transcription factors and their target genes form various patterns (called subgraphs or motifs) that are suspected of being of importance to how transcription factors exert their control of cellular processes. Zhang and colleagues have studied how a subset of transcription factors (called transcription hubs) utilizes such subgraphs in networks generated from yeast cells under various cellular states and environmental conditions. Their analyses show that different transcription hubs in the same network prefer different types of subgraphs, and that these preferences are not governed by subgraph frequencies in the network. They further show that when cellular conditions change, the transcription hubs frequently change their subgraph preferences, indicating that different modes of control require different types of subgraph use. These findings could have implications for our understanding of the mechanisms that underlie the fine-tuned control systems that govern a cell or an organism.