論文 - 詳細
| RRC ID | 48046 |
|---|---|
| 著者 | Ando H, Aoyama C, Horibata Y, Satou M, Mitsuhashi S, Itoh M, Hosaka K, Sugimoto H. |
| タイトル | Transcriptional suppression of CTP:phosphoethanolamine cytidylyltransferase by 25-hydroxycholesterol is mediated by nuclear factor-Y and Yin Yang 1. |
| ジャーナル | Biochem J |
| Abstract |
Pcyt2 (CTP:phosphoethanolamine cytidylyltransferase) is the rate-limiting enzyme in mammalian PE (phosphatidylethanolamine) biosynthesis. Previously, we reported that Pcyt2 mRNA levels increased in several types of cells after serum starvation, an effect that could be suppressed by supplementation with low-density lipoprotein or 25-HC (25-hydroxycholesterol). Transcription of Hmgcr, which encodes 3-hydroxy-3-methylglutaryl-CoA reductase, is also suppressed by 25-HC in the same dose-dependent manner. Nevertheless, a sterol-regulatory element was not detected in the Pcyt2 promoter region. The important element for transcriptional control of Pcyt2 by 25-HC (1.25 μM) was determined to reside between -56 and -36 on the basis of analysis with several Pcyt2 promoter deletion-luciferase reporters in NIH 3T3 cells. Using the yeast one-hybrid system, we found that NF-Y (nuclear factor-Y) binds at C(-37)CAAT(-41) and YY1 (Yin Yang1) binds at C(-42)AT(-40) in the Pcyt2 promoter. Endogenous NF-Y and YY1 bind clearly and competitively to these sites and are important for basal Pcyt2 transcription. Moreover, NF-Y binds to the Hmgcr promoter at C(-14)CA(-12) in gel-shift analysis, and suppression of the basal luciferase activity of the Hmgcr promoter-reporter construct (-30/+61) by 25-HC was abolished when C(-14)CA(-12) was mutated. Furthermore, transcriptional suppression of Pcyt2 by 25-HC was reduced following knockdown targeting of NF-YA or YY1. ChIP analysis revealed that 25-HC inhibited the interaction between NF-Y and RNA polymerase II on the Pcyt2 and Hmgcr promoters. On the basis of these results, we conclude that NF-Y and YY1 are important for the basal transcription of Pcyt2 and that NF-Y is involved in the inhibitory effects of 25-HC on Pcyt2 transcription. |
| 巻・号 | 471(3) |
| ページ | 369-79 |
| 公開日 | 2015-11-1 |
| DOI | 10.1042/BJ20150318 |
| PII | BJ20150318 |
| PMID | 26310456 |
| MeSH | Animals CCAAT-Binding Factor / genetics CCAAT-Binding Factor / metabolism* DNA-Binding Proteins / genetics Humans Hydroxycholesterols / administration & dosage Hydroxycholesterols / metabolism Hydroxymethylglutaryl CoA Reductases / biosynthesis Mice NIH 3T3 Cells Promoter Regions, Genetic RNA Nucleotidyltransferases / genetics* Transcription, Genetic / drug effects* YY1 Transcription Factor / genetics YY1 Transcription Factor / metabolism* |
| IF | 4.097 |
| 引用数 | 3 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | NIH3T3-3-4(RCB1862) |