The orphan nuclear receptor NOR-1 interacts with the homeobox containing protein Six3.
Neuron-derived orphan receptor 1 (NOR-1) is a member of the NGFI-B subfamily within the nuclear receptor superfamily. In order to identify cofactors that associate with NOR-1 in the fetal forebrain, we tested a yeast two-hybrid system with the NOR-1 cDNA fragment lacking a transactivating domain as a bait. By screening ... of the rat fetal brain embryonic day 17 library, a rat homologue of Six3 was identified as an associated protein. We demonstrated that NOR-1 interacted with Six3 in yeast and in vitro, and the association was required for the DNA binding and AF2 domains of NOR-1. Regarding the other members of the family (NGFI-B and RNR-1), association with Six3 was not observed in yeast. In addition, cotransfection experiments with Six3 and NOR-1 indicated that Six3 had a negative activity against the transactivation by NOR-1 through the NBRE response element in a dose-dependent manner. The overlap in expression of NOR-1 and Six3 was mainly detected in the rat fetal forebrain on embryonic day 18. Thereafter, the expression of both genes diminished rapidly. These results suggest that a dimer consisting of a homeobox containing protein Six3 and transcriptional factor NOR-1 might regulate gene expression during the late stage of the fetal forebrain development. This study provides, after the association of Ftz and Ftz-F1 in Drosophila, another example of a dimer formation of a homeobox protein and an orphan nuclear receptor.
Mesh Terms:
Amino Acid Sequence, Animals, DNA-Binding Proteins, Eye Proteins, Gene Expression Regulation, Developmental, Genes, Homeobox, Homeodomain Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Nuclear Receptor Subfamily 4, Group A, Member 1, Prosencephalon, Protein Structure, Tertiary, RNA, Messenger, Rats, Rats, Sprague-Dawley, Receptors, Cytoplasmic and Nuclear, Receptors, Steroid, Transcription Factors
Amino Acid Sequence, Animals, DNA-Binding Proteins, Eye Proteins, Gene Expression Regulation, Developmental, Genes, Homeobox, Homeodomain Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Nuclear Receptor Subfamily 4, Group A, Member 1, Prosencephalon, Protein Structure, Tertiary, RNA, Messenger, Rats, Rats, Sprague-Dawley, Receptors, Cytoplasmic and Nuclear, Receptors, Steroid, Transcription Factors
Dev. Neurosci.
Date: Feb. 15, 2001
PubMed ID: 11173923
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