RGD Reference Report - Transcriptional regulation of P450scc gene expression in the embryonic rodent nervous system. - Rat Genome Database

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Transcriptional regulation of P450scc gene expression in the embryonic rodent nervous system.

Authors: Hammer, F  Compagnone, NA  Vigne, JL  Bair, SR  Mellon, SH 
Citation: Hammer F, etal., Endocrinology 2004 Feb;145(2):901-12. Epub 2003 Oct 23.
RGD ID: 1300423
Pubmed: PMID:14576192   (View Abstract at PubMed)
DOI: DOI:10.1210/en.2003-0125   (Journal Full-text)

Steroid hormones are synthesized in adrenals, gonads, placenta, and the central and peripheral nervous systems (neurosteroids). Neurosteroidogenesis, like conventional steroidogenesis, begins with the conversion of cholesterol to pregnenolone, catalyzed by mitochondrial P450 side-chain cleavage enzyme (P450scc). Transcription of the P450scc gene in the adrenals and gonads requires steroidogenic factor-1, which is not expressed in the nervous system cells that express P450scc. A crucial transcriptional regulatory region of the rat P450scc gene is at -130/-94. We have purified two nuclear proteins (70 and 86 kDa) from rat glial C6 cells that specifically bind to the -130/-94 region of the rat P450scc promoter and identified them as the DNA-binding subunits of autoimmune antigen Ku. Ku colocalized with P450scc in several regions of the nervous system, but its overexpression in C6 cells did not augment transcription from a -130/-94 Luciferase construct. Members of the Sp family of transcription factors also bind to the same DNA sequence as Ku. Sp4 and Sp2 colocalize with P450scc in the nervous system early in development, whereas Sp1 and Sp4 colocalize later in development. Sp1 robustly increased transcription from this element in Sp-deficient Drosophila SL2 cells, and Ku synergistically enhanced this Sp1-stimulated transcription. Thus, members of the Sp transcription family play a role in activating P450scc gene transcription in the nervous system, and Ku may further augment this activation.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein-containing complex  IDA 1300423; 1300423 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
double-stranded DNA binding contributes_toIDA 1300423; 1300423 RGD 
protein binding  IPIXrcc6 (Rattus norvegicus)1300423 RGD 
protein binding  IPIXrcc5 (Rattus norvegicus)1300423 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Xrcc5  (X-ray repair cross complementing 5)
Xrcc6  (X-ray repair cross complementing 6)

Objects referenced in this article
Gene Xrcc5 X-ray repair complementing defective repair in Chinese hamster cells 5 Mus musculus
Gene Xrcc6 X-ray repair complementing defective repair in Chinese hamster cells 6 Mus musculus
Gene Cyp11a1 cytochrome P450, family 11, subfamily a, polypeptide 1 Rattus norvegicus
Gene Sp1 Sp1 transcription factor Rattus norvegicus
Gene Sp4 Sp4 transcription factor Rattus norvegicus

Additional Information