Article ; Online: Limits to a classic paradigm: most transcription factors in E. coli regulate genes involved in multiple biological processes.
2019 Volume 47, Issue 13, Page(s) 6656–6667
Abstract: Transcription factors (TFs) are important drivers of cellular decision-making. When bacteria encounter a change in the environment, TFs alter the expression of a defined set of genes in order to adequately respond. It is commonly assumed that genes ... ...
| Abstract | Transcription factors (TFs) are important drivers of cellular decision-making. When bacteria encounter a change in the environment, TFs alter the expression of a defined set of genes in order to adequately respond. It is commonly assumed that genes regulated by the same TF are involved in the same biological process. Examples of this are methods that rely on coregulation to infer function of not-yet-annotated genes. We have previously shown that only 21% of TFs involved in metabolism regulate functionally homogeneous genes, based on the proximity of the gene products' catalyzed reactions in the metabolic network. Here, we provide more evidence to support the claim that a 1-TF/1-process relationship is not a general property. We show that the observed functional heterogeneity of regulons is not a result of the quality of the annotation of regulatory interactions, nor the absence of protein-metabolite interactions, and that it is also present when function is defined by Gene Ontology terms. Furthermore, the observed functional heterogeneity is different from the one expected by chance, supporting the notion that it is a biological property. To further explore the relationship between transcriptional regulation and metabolism, we analyzed five other types of regulatory groups and identified complex regulons (i.e. genes regulated by the same combination of TFs) as the most functionally homogeneous, and this is supported by coexpression data. Whether higher levels of related functions exist beyond metabolism and current functional annotations remains an open question. |
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| MeSH term(s) | Enzymes/genetics ; Enzymes/physiology ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Escherichia coli Proteins/physiology ; Gene Expression Regulation, Bacterial ; Gene Ontology ; Gene Regulatory Networks/genetics ; Gene Regulatory Networks/physiology ; Metabolic Networks and Pathways ; Regulon/genetics ; Regulon/physiology ; Transcription Factors/physiology |
| Chemical Substances | Enzymes ; Escherichia coli Proteins ; Transcription Factors |
| Language | English |
| Publishing date | 2019-06-08 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 186809-3 |
| ISSN | 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048 |
| ISSN (online) | 1362-4962 ; 1362-4954 |
| ISSN | 0301-5610 ; 0305-1048 |
| DOI | 10.1093/nar/gkz525 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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