title: NF-κB oscillations translate into functionally related patterns of gene expression.
abstract: Several transcription factors (TFs) oscillate, periodically relocating between the cytoplasm and the nucleus. NF-κB, which plays key roles in inflammation and cancer, displays oscillations whose biological advantage remains unclear. Recent work indicated that NF-κB displays sustained oscillations that can be entrained, that is, reach a persistent synchronized state through small periodic perturbations. We show here that for our GFP-p65 knock-in cells NF-κB behaves as a damped oscillator able to synchronize to a variety of periodic external perturbations with no memory. We imposed synchronous dynamics to prove that transcription of NF-κB-controlled genes also oscillates, but mature transcript levels follow three distinct patterns. Two sets of transcripts accumulate fast or slowly, respectively. Another set, comprising chemokine and chemokine receptor mRNAs, oscillates and resets at each new stimulus, with no memory of the past. We propose that TF oscillatory dynamics is a means of segmenting time to provide renewing opportunity windows for decision.
authors.affiliation: Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.|San Raffaele University, Milan, Italy.
authors.forename: Samuel
authors.initials: S
authors.lastname: Zambrano
authors.affiliation: San Raffaele University, Milan, Italy.
authors.forename: Ilario
authors.initials: I
authors.lastname: De Toma
authors.affiliation: San Raffaele University, Milan, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Piffer
authors.affiliation: Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.|San Raffaele University, Milan, Italy.
authors.forename: Marco E
authors.identifier: http://orcid.org/0000-0002-5329-6445
authors.initials: ME
authors.lastname: Bianchi
authors.affiliation: Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Alessandra
authors.identifier: http://orcid.org/0000-0001-5006-9506
authors.initials: A
authors.lastname: Agresti
mesh_terms: D000818:Animals; D002460:Cell Line; D005347:Fibroblasts / Q000502:physiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D016328:NF-kappa B
keywords: NF-kappaB; TNF-alpha; computational biology; evolutionary biology; genomics; mathematical modelling; mouse; single-cell imaging; synchronous oscillations; systems biology; transcription