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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.
This article was published in the following journal.
Name: Nucleic acids research
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A family of transcription factors that contain a single cut domain and a divergent homeodomain. They regulate gene networks by controlling the expression of other transcription factors and they play an important role in CELL DIFFERENTIATION and METABOLISM.
A family of basic helix-loop-helix transcription factors that control expression of a variety of GENES involved in CELL CYCLE regulation. E2F transcription factors typically form heterodimeric complexes with TRANSCRIPTION FACTOR DP1 or transcription factor DP2, and they have N-terminal DNA binding and dimerization domains. E2F transcription factors can act as mediators of transcriptional repression or transcriptional activation.
Transcription factors whose primary function is to regulate the rate in which RNA is transcribed.
Maf transcription factors are a family of basic-leucine zipper transcription factors that are closely related to V-MAF ONCOGENE PROTEIN. The C-MAF PROTO-ONCOGENE PROTEIN was the first mammalian Maf transcription factor identified, and now the family is known to include a variety of other Maf proteins such as MAFB TRANSCRIPTION FACTOR; MAFF TRANSCRIPTION FACTOR; MAFG TRANSCRIPTION FACTOR; and MAFK TRANSCRIPTION FACTOR.
A family of VERTEBRATE homeodomain proteins that share homology with orthodenticle protein, Drosophila. They regulate GENETIC TRANSCRIPTION and play an important role in EMBRYONIC DEVELOPMENT of the BRAIN.
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