title: Inferring genome-wide functional modulatory network: a case study on NF-κB/RelA transcription factor.
abstract: How different pathways lead to the activation of a specific transcription factor (TF) with specific effects is not fully understood. We model context-specific transcriptional regulation as a modulatory network: triplets composed of a TF, target gene, and modulator. Modulators usually affect the activity of a specific TF at the posttranscriptional level in a target gene-specific action mode. This action may be classified as enhancement, attenuation, or inversion of either activation or inhibition. As a case study, we inferred, from a large collection of expression profiles, all potential modulations of NF-κB/RelA. The predicted modulators include many proteins previously not reported as physically binding to RelA but with relevant functions, such as RNA processing, cell cycle, mitochondrion, ubiquitin-dependent proteolysis, and chromatin modification. Modulators from different processes exert specific prevalent action modes on distinct pathways. Modulators from noncoding RNA, RNA-binding proteins, TFs, and kinases modulate the NF-κB/RelA activity with specific action modes consistent with their molecular functions and modulation level. The modulatory networks of NF-κB/RelA in the context epithelial-mesenchymal transition (EMT) and burn injury have different modulators, including those involved in extracellular matrix (FBN1), cytoskeletal regulation (ACTN1), and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long intergenic nonprotein coding RNA, and tumor suppression (FOXP1) for EMT, and TXNIP, GAPDH, PKM2, IFIT5, LDHA, NID1, and TPP1 for burn injury.
authors.affiliation: 1 Department of Biochemistry and Molecular Biology, University of Texas Medical Branch , Galveston, Texas.
authors.forename: Xueling
authors.initials: X
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.forename: Allan R
authors.initials: AR
authors.lastname: Brasier
authors.forename: Andrzej S
authors.initials: AS
authors.lastname: Kudlicki
mesh_terms: D002056:Burns / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D015894:Genome, Human; D006801:Humans; D008957:Models, Genetic; D060066:Protein Interaction Maps; D051996:Transcription Factor RelA / Q000502:physiology*; D000091346:Tripeptidyl-Peptidase 1
chemical_list: C498143:RELA protein, human; D051996:Transcription Factor RelA; D000091346:Tripeptidyl-Peptidase 1; C000717267:TPP1 protein, human
keywords: NF-κB; integrative probabilistic model; modulator; modulatory network; transcription factor
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