Analysis of expression and structure of the rat GH-secretagogue/ghrelin receptor (Ghsr) gene: Roles of epigenetic modifications in transcriptional regulation

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:345

Article

Inoue, Hiroshi^1,2  Sakamoto, Yukiko¹  Kangawa, Natsumi¹  Kimura, Chizuko¹  Ogata, Tsutomu³  Fujieda, Kenji⁴  Qian, Zhi Rong⁵  Sano, Toshiaki⁵  Itakura, Mitsuo¹ 

[1] Univ Tokushima, Div Genet Informat, Inst Genome Res, Tokushima 7708503, Japan

[2] Univ Tokushima, Diabet Therapeut & Res Ctr, Tokushima 7708503, Japan

[3] Natl Res Inst Child Hlth & Dev, Dept Endocrinol & Metab, Tokyo, Japan

[4] Asahikawa Med Univ, Dept Pediat, Asahikawa, Hokkaido, Japan

[5] Univ Tokushima, Grad Sch, Inst Hlth Biosci, Dept Human Pathol, Tokushima 7708503, Japan

关键词: Growth hormone secretagogue receptor;    Ghrelin receptor;    Gene expression;    CpG island;    Promoter methylation;   

DOI  :  10.1016/j.mce.2011.06.034

来源: Elsevier

【 摘 要 】

In the current study, to elucidate the molecular basis of cell type-specific expression of the GH-secretagogue/ghrelin receptor type 1A (GHSR1A), we characterized the structure and putative promoter region of the rat Ghsr gene. We identified an alternative 5'-untranslated first exon that contains multiple transcription start sites, and confirmed a 200-bp sequence proximal to this exon to be sufficient for basal promoter activity. A promoter-associated CpG island conserved across different species was found to be hypomethylated in Ghsr1a-expressing cell lines, while being heavily methylated in non-expressing cells. In cells with low or absent Ghsr1a expression, treatment with demethylating agents activated Ghsr1a transcription. Chromatin immunoprecipitation assays demonstrated Ghsr1a-expressing cells to display active histone modifications, whereas repressive modifications were present exclusively in other cell types. These results suggest epigenetic modifications at GHSR to play important roles in determining GHSR1A expression and abundance, and therefore the consequent sensitivity of cells to ghrelin. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

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