J Immunol 2021 Nov 15;20710:2512-2520. doi: 10.4049/jimmunol.2100092.

Retroposition of the Long Transcript from Multiexon IFN-β Homologs in Ancestry Vertebrate Gave Rise to the Proximal Transcription Elements of Intronless IFN-β Promoter in Humans.

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IFN-β is a unique member of type I IFN in humans and contains four positive regulatory domains (PRDs), I-II-III-IV, in its promoter, which are docking sites for transcription factors IFN regulatory factor (IRF) 3/7, NF-κB, IRF3/7, and activating transcription factor 2/Jun proto-oncogene, respectively. In chicken IFN-β and zebrafish IFNφ1 promoters, a conserved PRD or PRD-like sequences have been reported. In this study, a type I IFN gene, named as xl-IFN1 in the amphibian model Xenopus laevis, was found to contain similar PRD-like sites, IV-III/I-II, in its promoter, and these PRD-like sites were proved to be functionally responsive to activating transcription factor 2/Jun proto-oncogene, IRF3/IRF7, and p65, respectively. The xl-IFN1, as IFNφ1 in zebrafish, was transcribed into a long and a short transcript, with the long transcript containing all of the transcriptional elements, including PRD-like sites and TATA box in its proximal promoter. A retroposition model was then proposed to explain the transcriptional conservation of IFNφ1, xl-IFN1, and IFN-β in chicken and humans.

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Species referenced: Xenopus tropicalis Xenopus laevis
Genes referenced: atf2 ifn1 irf7 jun rela