| Author/Editor | Rozman, Damjana; Fink, Martina; Fimia, Gian Maria; Sassone-Corsi, Paolo; Waterman, Michael R | |
| Title | Cyclic adenosine 3',5'-monophosphate (cAMP)/cAMP - responsive element modulator (CREM)-dependent regulation of cholesterogenic lanosterol 14alpha-demethylase (CYP51) in spermatids | |
| Type | članek | |
| Source | Mol Endocrinol | |
| Vol. and No. | Letnik 13, št. 11 | |
| Publication year | 1999 | |
| Volume | str. 1951-62 | |
| Language | eng | |
| Abstract | Lanosterol 14 alpha-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 CREM phi-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 CREMT 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/CREM phi-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 CREM phi from germ cell nuclear extracts binds to a confirm CYP51-CRE2 element while no SREBP-1 binding observed in germ cells. The two regulatory path-ways 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 (CREMT- 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 altemate routes to control expression of cholesterogenic genes. | |
| Descriptors | SPERMATIDS LANOSTEROL CYCLIC AMP CHOLESTEROL MICE TRANSCRIPTION, GENETIC GERM CELLS TESTIS HAPLOIDY GENE EXPRESSION REGULATION, ENZYMOLOGIC IN SITU HYBRIDIZATION RNA, MESSENGER |