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
リソース情報
ヒト・動物細胞 HeLa