論文 - 詳細
| RRC ID | 58083 |
|---|---|
| 著者 | Ando H, Horibata Y, Aoyama C, Shimizu H, Shinohara Y, Yamashita S, Sugimoto H. |
| タイトル | Side-chain oxysterols suppress the transcription of CTP: Phosphoethanolamine cytidylyltransferase and 3-hydroxy-3-methylglutaryl-CoA reductase by inhibiting the interaction of p300 and NF-Y, and H3K27 acetylation. |
| ジャーナル | J Steroid Biochem Mol Biol |
| Abstract |
CTP: phosphoethanolamine cytidylyltransferase (Pcyt2) is the rate-limiting enzyme in mammalian phosphatidylethanolamine (PE) biosynthesis. Previously, we reported that increasedPcyt2 mRNA levels after serum starvation are suppressed by 25-hydroxycholesterol (HC) (25-HC), and that nuclear factor-Y (NF-Y) is involved in the inhibitory effects. Transcription of Hmgcr, which encodes 3-hydroxy-3-methylglutaryl-CoA reductase, is suppressed in the same manner. However, no typical sterol regulatory element (SRE) was detected in the Pcyt2 promoter. We were therefore interested in the effect of 25-HC on the modification of histones and thus treated cells with histone acetyltransferase inhibitor (anacardic acid) or histone deacetylase inhibitor (trichostatin A). The suppressive effect of 25-HC on Pcyt2 and Hmgcr mRNA transcription was ameliorated by trichostatin A. Anacardic acid, 25-HC and 24(S)-HC suppressed their transcription by inhibiting H3K27 acetylation in their promoters as evaluated by chromatin immunoprecipitation (ChIP) assays. 27-HC, 22(S)-HC and 22(R)-HC also suppressed their transcription, but 7α-HC, 7β-HC, the synthetic LXR agonist T0901317 and cholesterol did not. Furthermore, 25-HC inhibited p300 recruitment to the Pcyt2 and Hmgcr promoters, and suppressed H3K27 acetylation. 25-HC in the medium was easily conducted into cells. Based on these results, we concluded that 25-HC (and other side-chain oxysterols) in the medium was easily transferred into cells, suppressed H3K27 acetylation via p300 recruitment on the NF-Y complex in the Pcyt2 and Hmgcr promoters, and then suppressed transcription of these genes although LXR is not involved. |
| 巻・号 | 195 |
| ページ | 105482 |
| 公開日 | 2019-12-1 |
| DOI | 10.1016/j.jsbmb.2019.105482 |
| PII | S0960-0760(19)30296-1 |
| PMID | 31580889 |
| MeSH | Acetylation / drug effects Animals CCAAT-Binding Factor / metabolism* Cell Line E1A-Associated p300 Protein / metabolism* Histones / metabolism* Humans Hydroxycholesterols / pharmacology* Hydroxymethylglutaryl CoA Reductases / genetics* Mice Promoter Regions, Genetic RNA Nucleotidyltransferases / genetics* Transcription, Genetic / drug effects |
| IF | 3.813 |
| 引用数 | 0 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 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 | HeLa |