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Functional conservation of interactions between a homeodomain cofactor and a mammalian FTZ‐F1 homologue
Author(s) -
Steffensen Knut R,
Holter Elin,
Båvner Ann,
Nilsson Maria,
PeltoHuikko Markku,
Tomarev Stanislav,
Treuter Eckardt
Publication year - 2004
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400147
Subject(s) - homeobox , cofactor , biology , microbiology and biotechnology , genetics , gene , biochemistry , transcription factor , enzyme
Nuclear receptors are master regulators of metazoan gene expression with crucial roles during development and in adult physiology. Fushi tarazu factor 1 (FTZ‐F1) subfamily members are ancient orphan receptors with homologues from Drosophila to human that regulate diverse gene expression programs important for developmental processes, reproduction and cholesterol homeostasis in an apparently ligand‐independent manner. Thus, developmental and tissue‐specific cofactors may be particularly important in modulating the transcriptional activities of FTZ‐F1 receptors. In Drosophila , the homeodomain protein Fushi tarazu acts as a cofactor for FTZ‐F1 (NR5A3), leading to the hypothesis that a similar type of homeodomain cofactor–nuclear receptor relationship might exist in vertebrates. In this study, we have identified and characterized the homeodomain protein Prox1 as a co‐repressor for liver receptor homologue 1 (LRH1/NR5A2), a master regulator of cholesterol homeostasis in mammals. Our study suggests that interactions between LRH1 and Prox1 may fulfil roles both during development of the enterohepatic system and in adult physiology of the liver.