Regulation of human sterol 27-hydroxylase gene (CYP27A1) by bile acids and hepatocyte nuclear factor 4alpha (HNF4alpha).
Humans; Cell Line; Transfection; Gene Expression Regulation/drug effects; Base Sequence; Binding Sites/genetics; Response Elements/genetics; Molecular Sequence Data; Mutation; Chenodeoxycholic Acid/pharmacology; Transcription Factors/genetics/*metabolism; Hepatocyte Nuclear Factor 4; Mutagenesis; *DNA-Binding Proteins; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Bile Acids and Salts/*pharmacology; Cholestanetriol 26-Monooxygenase; DNA/chemistry/genetics; Luciferases/genetics/metabolism; Phosphoproteins/genetics/*metabolism; Recombinant Fusion Proteins/genetics/metabolism; Steroid Hydroxylases/*genetics; DNA; Dose-Response Relationship; Drug; Cultured; Receptors; Tumor Cells; Cloning; Molecular; Sequence Analysis; Promoter Regions; Genetic/*genetics; Cytoplasmic and Nuclear/genetics/metabolism; Site-Directed
Mitochondrial sterol 27-hydroxylase (CYP27A1) catalyses sterol side-chain oxidation of bile acid synthesis from cholesterol, and the first reaction of the acidic bile acid biosynthetic pathway. Hydrophobic bile acids suppress human CYP27A1 gene reporter activity when assayed in human hepatocellular blastoma HepG2 cells. Bile acids also inhibit CYP27A1 reporter activity in human embryonic kidney 293 cells. A putative bile acid response element (BARE) was mapped to a region downstream of nt -147 of the human CYP27A1 gene, within which a binding site for a liver-specific nuclear receptor, HNF4alpha, is identified. HNF4alpha strongly stimulates CYP27A1 gene transcription and mutation of its binding site markedly reduced promoter activity. Results suggest that human CYP27A1 gene transcription is suppressed by bile acids and HNF4alpha plays a pivotal role in transcriptional regulation of this gene.
Chen Wenling; Chiang John Y L
Gene
2003
2003-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
APeg3, a novel paternally expressed gene 3 antisense RNA transcript specifically expressed in vasopressinergic magnocellular neurons in the rat supraoptic nucleus.
3' Untranslated Regions/genetics; Amino Acid; Animals; Antisense/*genetics/isolation & purification/*metabolism; Conserved Sequence/genetics; DNA-Binding Proteins/genetics/*metabolism; Gene Expression Regulation/*genetics; Genetic/genetics; Genomic Imprinting/genetics; Hypothalamo-Hypophyseal System/cytology/metabolism; Kruppel-Like Transcription Factors; Male; Messenger/genetics/metabolism; Molecular Sequence Data; Neurons/*metabolism; Nucleic Acid; Protein Kinases/genetics/*metabolism; Rats; RNA; Sequence Homology; Sprague-Dawley; Supraoptic Nucleus/cytology/*metabolism; Transcription; Transcription Factors/genetics/*metabolism; Vasopressins/*metabolism; Water-Electrolyte Balance/genetics
Vasopressin (VP) and oxytocin (OT) play critical roles in the regulation of salt and water balance, lactation, and various behaviors and are expressed at very high levels in specific magnocellular neurons (MCNs) in the hypothalamo-neurohypophysial system (HNS). In addition to the cell-specific expression of the VP and OT genes in these cells, there are other transcripts that are preferentially expressed in the VP or OT MCNs. One such gene, paternally expressed gene 3 (Peg3), is an imprinted gene expressed exclusively from the paternal allele that encodes a Kruppel-type zinc finger-containing protein involved in maternal behavior and is abundantly expressed in the VP-MCNs. We report here the robust expression in the VP-MCNs of an RNA, which we designate APeg3 that is transcribed in the antisense direction to the 3' untranslated region of the Peg3 gene. The APeg3 mRNA is about 1 kb in size, and the full-length sequence of APeg3, as determined by 5' and 3' RACE, contains an open reading frame that predicts a protein of 93 amino acids and is predominantly expressed in VP-MCNs. Both Peg3 and APeg3 gene expression in the VP-MCNs increase during systemic hyperosmolality in vivo, demonstrating that both of these genes are osmoregulated.
Glasgow Eric; Ryu Seung-Lim; Yamashita Mitsuo; Zhang Bing-Jun; Mutsuga Noriko; Gainer Harold
Brain research. Molecular brain research
2005
2005-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.molbrainres.2005.02.030" target="_blank" rel="noreferrer noopener">10.1016/j.molbrainres.2005.02.030</a>
Coordinate down-regulation of cartilage matrix gene expression in Bcl-2 deficient chondrocytes is associated with decreased SOX9 expression and decreased mRNA stability.
Aggrecans; Animals; C-Type; Cell Line; Chondrocytes/*physiology; Collagen Type II/genetics/metabolism; Dactinomycin; Down-Regulation; Extracellular Matrix Proteins/analysis/genetics/*metabolism; Gene Expression Regulation; Glycoproteins/analysis/genetics/*metabolism; High Mobility Group Proteins/genetics/*metabolism; Lectins; Matrilin Proteins; Messenger/analysis/biosynthesis; Polymerase Chain Reaction/methods; Proteoglycans/genetics/metabolism; Proto-Oncogene Proteins c-bcl-2/deficiency/genetics/*physiology; Rats; RNA; RNA Stability; Signal Transduction; SOX9 Transcription Factor; Transcription Factors/genetics/*metabolism; Transfection
The anti-apoptotic protein Bcl-2 has been shown to function in roles unrelated to apoptosis in a variety of cell types. We have previously reported that loss of Bcl-2 expression alters chondrocyte morphology and modulates aggrecan expression via an apoptosis-independent pathway. Here we show that Bcl-2 is required for chondrocytes to maintain expression of a variety of cartilage-specific matrix proteins. Using quantitative, real-time PCR, we demonstrate that Bcl-2-deficient chondrocytes coordinately down-regulate genes coding for hyaline cartilage matrix proteins including collagen II, collagen IX, aggrecan, and link protein. The decrease in steady-state level of these mRNA transcripts results, in part, from decreased mRNA stability in Bcl-2-deficient chondrocytes. Transcriptional regulation is also likely involved because chondrocytes with decreased Bcl-2 levels show decreased expression of SOX9, a transcription factor necessary for expressing the major cartilage matrix proteins. In contrast, chondrocytes constitutively expressing Bcl-2 have a stable phenotype when subjected to loss of serum factor signaling. These cells maintain high levels of SOX9, as well as the SOX9 targets collagen II and aggrecan. These results suggest that Bcl-2 is involved in a pathway important for maintaining a stable chondrocyte phenotype.
Kinkel Mary D; Horton Walter E Jr
Journal of cellular biochemistry
2003
2003-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/jcb.10442" target="_blank" rel="noreferrer noopener">10.1002/jcb.10442</a>