title: Evolution of a tissue-specific silencer underlies divergence in the expression of pax2 and pax8 paralogues.
abstract: Recent studies underscore a role for the differential degeneration of enhancers in the evolutionary diversification of paralogue expression. However, no one has reported evidence for the involvement of innovative cis-regulatory changes. Here we show that silencer innovation diversified expression of the vertebrate paralogues, pax2 and pax8. pax2 shows multi-tissue expression, as does the ancestral amphioxus orthologue, pax2/5/8, whereas pax8 expression localizes to a subset of pax2-expressing tissues. We reveal that both pax2 and pax8 retain ancestral enhancers capable of directing pax2-like, multi-tissue expression. However, a silencer within the pax8 proximal promoter suppresses pleiotropic enhancer activity outside the pax8-expressing tissues. In contrast, the combination of the pax2 proximal promoter with either the pax8 or pax2 enhancer recapitulates pax2-like expression, as in the amphioxus pax2/5/8 promoter. We propose that silencer innovation, rather than enhancer degeneration, was crucial for the divergent expression of paralogues with pleiotropic enhancers inherited from their common progenitor.
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5, Takayama, Ikoma, 630-0192, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Ochi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tamai
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nagano
authors.forename: Akane
authors.initials: A
authors.lastname: Kawaguchi
authors.forename: Norihiro
authors.initials: N
authors.lastname: Sudou
authors.forename: Hajime
authors.initials: H
authors.lastname: Ogino
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004742:Enhancer Elements, Genetic / Q000235:genetics; D006801:Humans; D051762:PAX2 Transcription Factor / Q000378:metabolism*; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014714:Vertebrates; D014981:Xenopus
chemical_list: D051762:PAX2 Transcription Factor; D051761:Paired Box Transcription Factors