Hippocampal Expression of the Orphan Nuclear Receptor Gene hzf-3/nurr1 during Spatial Discrimination Learning

The orphan nuclear receptor Rev-erbα (NR1D1) plays an important role in the regulation of the circadian pacemaker and its expression has been shown to be regulated with a robust circadian rhythm in zebrafish and mammals. In addition, in zebrafish its expression has been shown to be developmentally regulated. In order to analyze the mechanisms of the zfRev-erbα gene regulation, we have isolated its 5′-upstream region. We found that two promoters control the zfRev-erbα expression. The first one (ZfP1) is characterized by a very high degree of sequence identity with the mammalian P1 promoter and contains, as the mammalian P1, a functional Rev-erbα-binding site (RevDR2). Inhibition of zfRev-erbα activity in zebrafish embryos using antisense-morpholino knockdown results in an increase of zfRev-erbα gene expression suggesting that zfRev-erbα is repressing its own transcription in vivo. In addition, we show that ROR orphan receptors also regulate in vitro and in vivo zfRev-erbα gene expression through the same RevDR2 element. In contrast, the second promoter ZfP2 is strikingly different from the mammalian P2: its sequence is not conserved between zebrafish and mammals and is not regulated by the same transcription factors. Together, these data suggest that ZfP1 is orthologous to the mammalian P1 promoter, whereas zebrafish ZfP2 has no mammalian ortholog and does not function like ZfP1 to control Rev-erbα expression.

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The Mouse Adrenocorticotropin Receptor Gene: Cloning and Characterization of Its Promoter and Evidence for a Role for the Orphan Nuclear Receptor Steroidogenic Factor 1

Molecular Endocrinology ◽

10.1210/mend.11.7.9938 ◽

1997 ◽

Vol 11 (7) ◽

pp. 867-876 ◽

Cited By ~ 31

Author(s):

Florence M. Cammas ◽

Gill D. Pullinger ◽

Stewart Barker ◽

Adrian J. L. Clark

Keyword(s):

Gene Cloning ◽

Nuclear Receptor ◽

Receptor Gene ◽

Orphan Nuclear Receptor ◽

Steroidogenic Factor 1 ◽

Gene Cloning And Characterization

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Expression of the Mouse Gonadotropin-Releasing Hormone Receptor Gene in αT3-1 Gonadotrope Cells Is Stimulated by Cyclic 3′,5′-Adenosine Monophosphate and Protein Kinase A, and Is Modulated by Steroidogenic Factor-1 and Nur77

Endocrinology ◽

10.1210/en.2002-220874 ◽

2003 ◽

Vol 144 (5) ◽

pp. 1958-1971 ◽

Cited By ~ 20

Author(s):

Hanél Sadie ◽

Gustav Styger ◽

Janet Hapgood

Keyword(s):

Protein Kinase ◽

Protein Kinase A ◽

Nuclear Receptor ◽

Receptor Gene ◽

Control Point ◽

Negative Regulator ◽

Mrna Levels ◽

Orphan Nuclear Receptor ◽

Steroidogenic Factor 1 ◽

Kinase A

Regulation of GnRH receptor (GnRHR) expression levels in the pituitary is a crucial control point in reproduction. The promoter of the mouse GnRHR gene contains nuclear receptor half-sites (NRS) at –244/−236 and −15/−7 relative to the translation start site. Although binding of steroidogenic factor-1 (SF-1) to the –244/−236NRS is implicated in mediating basal and gonadotrope-specific expression, no function or protein-DNA interactions have previously been described for the –15/−7NRS. We report that levels of the endogenous GnRHR mRNA in αT3-1 cells are stimulated by forskolin and 8-bromo-cAMP. We also show that the orphan nuclear receptor Nur77 is expressed in αT3-1 cells, and that both SF-1 and Nur77 bind to the –15/−7NRS and –244/−236NRS in vitro. We show that the activity of the proximal (−579/+1) mouse GnRHR promoter is up-regulated by protein kinase A, via a mechanism that is modulated by SF-1, both positively and negatively, through binding to the –244/−236NRS or the –15/−7NRS, respectively. Nur77 appears to be capable of acting as a negative regulator of this response, via the –15/−7NRS. Furthermore, we show that forskolin up-regulates SF-1 mRNA levels in αT3-1 cells, indicating that the levels of SF-1 play a role in modulating the protein kinase A response.

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The Divergent Orphan Nuclear Receptor ODR-7 Regulates Olfactory Neuron Gene Expression via Multiple Mechanisms in Caenorhabditis elegans

Genetics ◽

10.1093/genetics/165.4.1779 ◽

2003 ◽

Vol 165 (4) ◽

pp. 1779-1791

Author(s):

Marc E Colosimo ◽

Susan Tran ◽

Piali Sengupta

Keyword(s):

Nuclear Receptors ◽

Nuclear Receptor ◽

Molecular Mechanisms ◽

Target Genes ◽

Receptor Gene ◽

Biological Processes ◽

Orphan Nuclear Receptor ◽

Olfactory Neurons ◽

C Elegans

Abstract Nuclear receptors regulate numerous critical biological processes. The C. elegans genome is predicted to encode ∼270 nuclear receptors of which >250 are unique to nematodes. ODR-7 is the only member of this large divergent family whose functions have been defined genetically. ODR-7 is expressed in the AWA olfactory neurons and specifies AWA sensory identity by promoting the expression of AWA-specific signaling genes and repressing the expression of an AWC-specific olfactory receptor gene. To elucidate the molecular mechanisms of action of a divergent nuclear receptor, we have identified residues and domains required for different aspects of ODR-7 function in vivo. ODR-7 utilizes an unexpected diversity of mechanisms to regulate the expression of different sets of target genes. Moreover, these mechanisms are distinct in normal and heterologous cellular contexts. The odr-7 ortholog in the closely related nematode C. briggsae can fully substitute for all ODR-7-mediated functions, indicating conservation of function across 25–120 million years of divergence.

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