PMID- 10051404
OWN - NLM
STAT- MEDLINE
DCOM- 19990422
LR  - 20161124
IS  - 0888-7543 (Print)
IS  - 0888-7543 (Linking)
VI  - 56
IP  - 2
DP  - 1999 Mar 1
TI  - Structure and chromosomal assignment of the sterol 12alpha-hydroxylase gene
      (CYP8B1) in human and mouse: eukaryotic cytochrome P-450 gene devoid of introns.
PG  - 184-96
AB  - Sterol 12alpha-hydroxylase (CYP8B1) is a hepatic cytochrome P-450 that controls
      the ratio of cholic acid over chenodeoxycholic acid in bile and thus controls the
      solubility of cholesterol. Both the human and the mouse CYP8B1 complementary DNA 
      and gene were cloned and structurally characterized. Surprisingly, the genomic
      DNA from both species was found to lack introns. The major transcript of the
      human gene was estimated to be 3950 bp, and the putative promoter region was
      estimated to be at least 1360 bp. The murine structural gene was found to span
      approximately 3 kb. By using FISH and radiation hybrid mapping techniques, the
      human CYP8B1 gene was located to chromosome 3p21.3-p22, whereas FISH mapped the
      murine counterpart to chromosome 9qF4, a region that is homologous to the third
      human chromosome. The results from the chromosome mapping and Southern blotting
      indicated that the gene is present in a single copy. Transcription of the mouse
      and human CYP8B1 genes was initiated from a position situated 51 and 35 bases,
      respectively, downstream of a consensus TATA box. A homology of 21% for the
      promoter regions of mouse and human may indicate differences in transcriptional
      regulation. Although a potent induction of CYP8B1 mRNA was observed upon
      starvation of mice, the mechanism behind this effect was not revealed by analysis
      of the promoter for potential cis-acting elements. In the human promoter, several
      possible cis-acting regions were identified but none of them could be directly
      related to bile acid metabolism. After transfection of COS cells with the human
      coding region, mRNA and enzymatic activity for the 12alpha-hydroxylase were
      identified. This is the first mammalian cytochrome P-450 gene reported to lack
      introns. The importance of this structural feature for evolution and gene
      regulation is discussed.
CI  - Copyright 1999 Academic Press.
FAU - Gafvels, M
AU  - Gafvels M
AD  - Division of Clinical Chemistry, Karolinska Institute at Huddinge University
      Hospital, Huddinge, S-141 86, Sweden.
FAU - Olin, M
AU  - Olin M
FAU - Chowdhary, B P
AU  - Chowdhary BP
FAU - Raudsepp, T
AU  - Raudsepp T
FAU - Andersson, U
AU  - Andersson U
FAU - Persson, B
AU  - Persson B
FAU - Jansson, M
AU  - Jansson M
FAU - Bjorkhem, I
AU  - Bjorkhem I
FAU - Eggertsen, G
AU  - Eggertsen G
LA  - eng
SI  - GENBANK/AF090317
SI  - GENBANK/AF090318
SI  - GENBANK/AF090319
SI  - GENBANK/AF090320
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Genomics
JT  - Genomics
JID - 8800135
RN  - 0 (DNA, Complementary)
RN  - 63231-63-0 (RNA)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.14.- (Steroid Hydroxylases)
RN  - EC 1.14.18.8 (Steroid 12-alpha-Hydroxylase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - COS Cells
MH  - Chromosome Banding
MH  - Chromosome Mapping
MH  - Chromosomes/genetics
MH  - Chromosomes, Human, Pair 3/genetics
MH  - Cytochrome P-450 Enzyme System/*genetics
MH  - DNA, Complementary/chemistry/genetics/isolation & purification
MH  - Eukaryotic Cells/metabolism
MH  - Gene Expression Regulation
MH  - Genes/genetics
MH  - Humans
MH  - Hybrid Cells
MH  - In Situ Hybridization, Fluorescence
MH  - Introns
MH  - Liver/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred Strains
MH  - Molecular Sequence Data
MH  - Promoter Regions, Genetic
MH  - RNA/genetics/metabolism
MH  - Rabbits
MH  - Regulatory Sequences, Nucleic Acid
MH  - Sequence Alignment
MH  - Sequence Analysis, DNA
MH  - Sequence Homology, Amino Acid
MH  - Steroid 12-alpha-Hydroxylase
MH  - Steroid Hydroxylases/*genetics
MH  - Transfection
EDAT- 1999/03/03 00:00
MHDA- 1999/03/03 00:01
CRDT- 1999/03/03 00:00
PHST- 1999/03/03 00:00 [pubmed]
PHST- 1999/03/03 00:01 [medline]
PHST- 1999/03/03 00:00 [entrez]
AID - S0888-7543(98)95606-3 [pii]
AID - 10.1006/geno.1998.5606 [doi]
PST - ppublish
SO  - Genomics. 1999 Mar 1;56(2):184-96. doi: 10.1006/geno.1998.5606.