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Article: Structure and mapping of the human lanosterol 14α-demethylase gene (CYP51) encoding the cytochrome p450 involved in cholesterol biosynthesis; comparison of exon/intron organization with other mammalian and fungal CYP genes

TitleStructure and mapping of the human lanosterol 14α-demethylase gene (CYP51) encoding the cytochrome p450 involved in cholesterol biosynthesis; comparison of exon/intron organization with other mammalian and fungal CYP genes
Authors
Issue Date1996
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ygeno
Citation
Genomics, 1996, v. 38 n. 3, p. 371-381 How to Cite?
AbstractSterol 14α-demethylase (P45014DM) encoded by CYP51 is a member of the cytochrome P450 (CYP) gene superfamily involved in sterol biosynthesis in fungi, plants, and animals. Constraints imposed by the specific function of CYP51 have severely limited sequence divergence in this family. Consequently, CYP51 is the only P460 family recognizable across all eukaryotic phyla. We have determined the structure of the functional human CYP51 gene, which spans 22 kb, is divided into 10 exons, and maps to 7q21.2-q21.3. The 5' portion of intron 1 is GC-rich and contains potential binding sites for several transcription factors. Primer extension studies reveal predominant transcription initiation sites in liver, kidney, lung, and placenta 250 and 249 bp upstream from the translation start site and a second major site at - 100 bp. Ubiquitous expression of human CYP51 (Stromstedt et al., Arch. Biochem. Biophys. 329: 73-81, 1996), the absence of TATA and CAAT patterns, a GC-rich sequence in the promoter region, and initiation of CYP51 transcription at more than one site indicate that CYP51 is a housekeeping gene. The 5'-flanking region, exon 1, and a portion of intron 1 show the characteristics of a CpG island, with the observed/expected CpG ratio of 0.79. Sterol responsive element-like motifs were present in this region, suggesting regulation by oxysterols via a mechanism similar to that associated with other genes involved in cholesterol homeostasis. Comparison of the human CYP51 gene structure with structures of other mammalian and fungal CYP gene families shows that 7 of the 9 CYP51 introns are located at unique positions. More than 80 intron locations exist in mammalian and fungal CYP gene families, and it seems very unlikely that all these introns could have been present in the primordial CYP gene.
Persistent Identifierhttp://hdl.handle.net/10722/44311
ISSN
2015 Impact Factor: 2.386
2015 SCImago Journal Rankings: 1.281
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorRozman, Den_HK
dc.contributor.authorStrömstedt, Men_HK
dc.contributor.authorTsui, LCen_HK
dc.contributor.authorScherer, SWen_HK
dc.contributor.authorWaterman, MRen_HK
dc.date.accessioned2007-09-12T03:51:11Z-
dc.date.available2007-09-12T03:51:11Z-
dc.date.issued1996en_HK
dc.identifier.citationGenomics, 1996, v. 38 n. 3, p. 371-381en_HK
dc.identifier.issn0888-7543en_HK
dc.identifier.urihttp://hdl.handle.net/10722/44311-
dc.description.abstractSterol 14α-demethylase (P45014DM) encoded by CYP51 is a member of the cytochrome P450 (CYP) gene superfamily involved in sterol biosynthesis in fungi, plants, and animals. Constraints imposed by the specific function of CYP51 have severely limited sequence divergence in this family. Consequently, CYP51 is the only P460 family recognizable across all eukaryotic phyla. We have determined the structure of the functional human CYP51 gene, which spans 22 kb, is divided into 10 exons, and maps to 7q21.2-q21.3. The 5' portion of intron 1 is GC-rich and contains potential binding sites for several transcription factors. Primer extension studies reveal predominant transcription initiation sites in liver, kidney, lung, and placenta 250 and 249 bp upstream from the translation start site and a second major site at - 100 bp. Ubiquitous expression of human CYP51 (Stromstedt et al., Arch. Biochem. Biophys. 329: 73-81, 1996), the absence of TATA and CAAT patterns, a GC-rich sequence in the promoter region, and initiation of CYP51 transcription at more than one site indicate that CYP51 is a housekeeping gene. The 5'-flanking region, exon 1, and a portion of intron 1 show the characteristics of a CpG island, with the observed/expected CpG ratio of 0.79. Sterol responsive element-like motifs were present in this region, suggesting regulation by oxysterols via a mechanism similar to that associated with other genes involved in cholesterol homeostasis. Comparison of the human CYP51 gene structure with structures of other mammalian and fungal CYP gene families shows that 7 of the 9 CYP51 introns are located at unique positions. More than 80 intron locations exist in mammalian and fungal CYP gene families, and it seems very unlikely that all these introns could have been present in the primordial CYP gene.en_HK
dc.languageengen_HK
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ygenoen_HK
dc.relation.ispartofGenomicsen_HK
dc.subject.meshCytochrome p-450 enzyme system - geneticsen_HK
dc.subject.meshFungi - geneticsen_HK
dc.subject.meshGenes, fungalen_HK
dc.subject.meshMammals - geneticsen_HK
dc.subject.meshOxidoreductases - geneticsen_HK
dc.titleStructure and mapping of the human lanosterol 14α-demethylase gene (CYP51) encoding the cytochrome p450 involved in cholesterol biosynthesis; comparison of exon/intron organization with other mammalian and fungal CYP genesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0888-7543&volume=38&issue=3&spage=371&epage=381&date=1996&atitle=Structure+and+mapping+of+the+human+lanosterol+14alpha-demethylase+gene+(CYP51)+encoding+the+cytochrome+P450+involved+in+cholesterol+biosynthesis;+comparison+of+exon/intron+organization+with+other+mammalian+and+fungal+CYP+genesen_HK
dc.identifier.emailTsui, LC: tsuilc@hkucc.hku.hken_HK
dc.identifier.authorityTsui, LC=rp00058en_HK
dc.description.naturelink_to_subscribed_fulltexten_HK
dc.identifier.doi10.1006/geno.1996.0640en_HK
dc.identifier.pmid8975714-
dc.identifier.scopuseid_2-s2.0-0030589679en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0030589679&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume38en_HK
dc.identifier.issue3en_HK
dc.identifier.spage371en_HK
dc.identifier.epage381en_HK
dc.identifier.isiWOS:A1996WB42900016-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridRozman, D=7003529432en_HK
dc.identifier.scopusauthoridStrömstedt, M=6602893325en_HK
dc.identifier.scopusauthoridTsui, LC=7102754167en_HK
dc.identifier.scopusauthoridScherer, SW=35374654500en_HK
dc.identifier.scopusauthoridWaterman, MR=7101793212en_HK

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