PMID- 10551787
OWN - NLM
STAT- MEDLINE
DCOM- 19991130
LR  - 20191210
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 13
IP  - 11
DP  - 1999 Nov
TI  - Cyclic adenosine 3',5'-monophosphate(cAMP)/cAMP-responsive element modulator
      (CREM)-dependent regulation of cholesterogenic lanosterol 14alpha-demethylase
      (CYP51) in spermatids.
PG  - 1951-62
AB  - 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.
FAU - Rozman, D
AU  - Rozman D
AD  - Institute of Biochemistry, Medical Center for Molecular Biology, Medical Faculty 
      University of Ljubljana, Slovenia. rozman@ibmi.mf.uni-lj.si
FAU - Fink, M
AU  - Fink M
FAU - Fimia, G M
AU  - Fimia GM
FAU - Sassone-Corsi, P
AU  - Sassone-Corsi P
FAU - Waterman, M R
AU  - Waterman MR
LA  - eng
GR  - DK-28350/DK/NIDDK NIH HHS/United States
GR  - ES 00267/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (CYP51A1 protein, human)
RN  - 0 (Cyp51 protein, rat)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (SREBF1 protein, human)
RN  - 0 (Srebf1 protein, mouse)
RN  - 0 (Srebf1 protein, rat)
RN  - 0 (Sterol Regulatory Element Binding Protein 1)
RN  - 0 (Sterols)
RN  - 0 (Transcription Factors)
RN  - 135844-64-3 (Cyclic AMP Response Element Modulator)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 1.14.14.154 (Cyp51 protein, mouse)
RN  - EC 1.14.14.154 (Sterol 14-Demethylase)
RN  - EC 2.5.1.21 (Farnesyl-Diphosphate Farnesyltransferase)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - *CCAAT-Enhancer-Binding Proteins
MH  - Cyclic AMP/*metabolism
MH  - Cyclic AMP Response Element Modulator
MH  - Cytochrome P-450 Enzyme System/*genetics/*metabolism
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - Farnesyl-Diphosphate Farnesyltransferase/metabolism
MH  - Gene Expression Profiling
MH  - Humans
MH  - Male
MH  - Mice
MH  - Molecular Sequence Data
MH  - Nuclear Proteins/metabolism
MH  - Oxidoreductases/*genetics/*metabolism
MH  - Promoter Regions, Genetic
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Repressor Proteins
MH  - Response Elements/*physiology
MH  - Spermatids/*metabolism
MH  - Sterol 14-Demethylase
MH  - Sterol Regulatory Element Binding Protein 1
MH  - Sterols/metabolism
MH  - Testis/physiology
MH  - *Transcription Factors
EDAT- 1999/11/07 00:00
MHDA- 1999/11/07 00:01
CRDT- 1999/11/07 00:00
PHST- 1999/11/07 00:00 [pubmed]
PHST- 1999/11/07 00:01 [medline]
PHST- 1999/11/07 00:00 [entrez]
AID - 10.1210/mend.13.11.0377 [doi]
PST - ppublish
SO  - Mol Endocrinol. 1999 Nov;13(11):1951-62. doi: 10.1210/mend.13.11.0377.