The dependence of expression of NF-κB-dependent genes: statistics and evolutionary conservation of control sequences in the promoter and in the 3' UTR.
Abstract
The NF-κB family plays a prominent role in the innate immune response, cell cycle activation or cell apoptosis. Upon stimulation by pathogen-associated patterns, such as viral RNA a kinase cascade is activated, which strips the NF-κB of its inhibitor IκBα molecule and allows it to translocate into the nucleus. Once in the nucleus, it activates transcription of approximately 90 genes whose kinetics of expression differ relative to when NF-κB translocates into the nucleus, referred to as Early, Middle and Late genes. It is not obvious what mechanism is responsible for segregation of the genes' timing of transcriptional response. It is likely that the differences in timing are due, in part, to the number and type of transcription factor binding sites (TFBS), required for NF-κB itself as well as for the putative cofactors, in the Early versus Late genes. We therefore applied an evolutionary analysis of conserved TFBS. We also examined whether transcription dynamic was related to the presence of AU-rich elements (ARE) located in 3'UTR of the mRNA because recent studies have shown that the presence of AREs is associated with rapid gene induction. We found that Early genes were significantly enriched in NF-κB binding sites occurring i...Continue Reading
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oPOSSUM: identification of over-represented transcription factor binding sites in co-expressed genes
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Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis