Role of Rev-erbα domains for transactivation of the connexin43 promoter with Sp1

Hiromitsu Negoro; Takeshi Okinami; Akihiro Kanematsu; Masaaki Imamura; Yasuhiko Tabata; Osamu Ogawa

doi:10.1016/j.febslet.2012.11.021

Role of Rev-erbα domains for transactivation of the connexin43 promoter with Sp1

FEBS Lett. 2013 Jan 4;587(1):98-103. doi: 10.1016/j.febslet.2012.11.021. Epub 2012 Nov 28.

Authors

Hiromitsu Negoro¹, Takeshi Okinami, Akihiro Kanematsu, Masaaki Imamura, Yasuhiko Tabata, Osamu Ogawa

Affiliation

¹ Department of Urology, Kyoto University, Graduate School of Medicine, Sakyo, Kyoto 606-8507, Japan.

PMID: 23201262
DOI: 10.1016/j.febslet.2012.11.021

Abstract

Rev-erbα, a component of the circadian clock, has also been known as a nuclear receptor that lacks activation function domain 2, functioning as a ligand-dependent transcriptional repressor. However, we recently reported that Rev-erbα activates connexin43 transcription by forming a complex with Sp1. Here we show that heme, a REV-ERB ligand, is dispensable for this novel mechanism and that Rev-erbβ, having homologies with Rev-erbα, does not activate connexin43, but competes with the Rev-erbα/Sp1. The A/B region of Rev-erbα, which is not conserved in Rev-erbβ, is a crucial activating domain, while the ligand binding domain, conserved in Rev-erbβ, functions as a competitor.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Binding, Competitive
Connexin 43 / chemistry
Connexin 43 / genetics
Connexin 43 / metabolism*
Gene Deletion
Genes, Reporter
HEK293 Cells
Heme / metabolism
Humans
Ligands
Mice
Mutagenesis, Insertional
Mutagenesis, Site-Directed
Mutant Proteins / chemistry
Mutant Proteins / metabolism
Nuclear Receptor Subfamily 1, Group D, Member 1 / chemistry
Nuclear Receptor Subfamily 1, Group D, Member 1 / genetics
Nuclear Receptor Subfamily 1, Group D, Member 1 / metabolism*
Promoter Regions, Genetic*
Protein Interaction Domains and Motifs
Receptors, Cytoplasmic and Nuclear / chemistry
Receptors, Cytoplasmic and Nuclear / genetics
Receptors, Cytoplasmic and Nuclear / metabolism
Recombinant Proteins / chemistry
Recombinant Proteins / metabolism
Repressor Proteins / chemistry
Repressor Proteins / genetics
Repressor Proteins / metabolism
Sp1 Transcription Factor / genetics
Sp1 Transcription Factor / metabolism*
Transcriptional Activation*

Substances

Connexin 43
GJA1 protein, mouse
Ligands
Mutant Proteins
Nr1d1 protein, mouse
Nr1d2 protein, mouse
Nuclear Receptor Subfamily 1, Group D, Member 1
Receptors, Cytoplasmic and Nuclear
Recombinant Proteins
Repressor Proteins
Sp1 Transcription Factor
Heme