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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
1999-11-30
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pubmed:abstractText |
Lanosterol 14alpha-demethylase (CYP51) produces MAS sterols, intermediates in cholesterol biosynthesis that can reinitiate meiosis in mouse oocytes. As a cholesterogenic gene, CYP51 is regulated by a sterol/sterol-regulatory element binding protein (SREBP)-dependent pathway in liver and other somatic tissue. In testis, however, cAMP/cAMP-responsive element modulator CREMtau-dependent regulation of CYP51 predominates, leading to increased levels of shortened CYP51 mRNA transcripts. CREM-/- mice lack the abundant germ cell-specific CYP51 mRNAs in testis while expression of somatic CYP51 transcripts is unaffected. The mRNA levels of squalene synthase (an enzyme preceding CYP51 in cholesterol biosynthesis in testis of CREM-/- mice are unchanged as compared with wild-type animals, showing that regulation by CREMtau is not characteristic for all cholesterogenic genes expressed during spermatogenesis. The -334/+314 bp CYP51 region can mediate both the sterol/SREBP-dependent as well as the cAMP/CREMtau-dependent transcriptional activation. SREBP-1a from somatic cell nuclear extracts binds to a conserved CYP51-SRE1 element in the CYP51 proximal promoter. The cAMP-dependent transcriptional activator CREMtau from germ cell nuclear extracts binds to a conserved CYP51-CRE2 element while no SREBP-1 binding is observed in germ cells. The two regulatory pathways mediating expression of CYP51 describe this gene as a cholesterogenic gene (SREBP-dependent expression in liver and other somatic cells) and also as a haploid expressed gene (CREMtau-dependent expression in haploid male germ cells). While in somatic cells all genes involved in cholesterol biosynthesis are regulated coordinately by the sterol/SREBP-signaling pathway, male germ cells contain alternate routes to control expression of cholesterogenic genes.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/CYP51A1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response Element...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyp51 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cyp51 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Farnesyl-Diphosphate...,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidoreductases,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SREBF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Srebf1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Srebf1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Sterol 14-Demethylase,
http://linkedlifedata.com/resource/pubmed/chemical/Sterol Regulatory Element Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Sterols,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0888-8809
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1951-62
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:10551787-Animals,
pubmed-meshheading:10551787-Base Sequence,
pubmed-meshheading:10551787-CCAAT-Enhancer-Binding Proteins,
pubmed-meshheading:10551787-Cyclic AMP,
pubmed-meshheading:10551787-Cyclic AMP Response Element Modulator,
pubmed-meshheading:10551787-Cytochrome P-450 Enzyme System,
pubmed-meshheading:10551787-DNA-Binding Proteins,
pubmed-meshheading:10551787-Farnesyl-Diphosphate Farnesyltransferase,
pubmed-meshheading:10551787-Gene Expression Profiling,
pubmed-meshheading:10551787-Humans,
pubmed-meshheading:10551787-Male,
pubmed-meshheading:10551787-Mice,
pubmed-meshheading:10551787-Molecular Sequence Data,
pubmed-meshheading:10551787-Nuclear Proteins,
pubmed-meshheading:10551787-Oxidoreductases,
pubmed-meshheading:10551787-Promoter Regions, Genetic,
pubmed-meshheading:10551787-Rats,
pubmed-meshheading:10551787-Rats, Sprague-Dawley,
pubmed-meshheading:10551787-Repressor Proteins,
pubmed-meshheading:10551787-Response Elements,
pubmed-meshheading:10551787-Spermatids,
pubmed-meshheading:10551787-Sterol 14-Demethylase,
pubmed-meshheading:10551787-Sterol Regulatory Element Binding Protein 1,
pubmed-meshheading:10551787-Sterols,
pubmed-meshheading:10551787-Testis,
pubmed-meshheading:10551787-Transcription Factors
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pubmed:year |
1999
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pubmed:articleTitle |
Cyclic adenosine 3',5'-monophosphate(cAMP)/cAMP-responsive element modulator (CREM)-dependent regulation of cholesterogenic lanosterol 14alpha-demethylase (CYP51) in spermatids.
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pubmed:affiliation |
Institute of Biochemistry, Medical Center for Molecular Biology, Medical Faculty University of Ljubljana, Slovenia. rozman@ibmi.mf.uni-lj.si
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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