Retinoic acid stimulates transcription of the rat SHARP-2 gene via multiple pathways

Retinoic acid stimulates transcription of the rat SHARP-2 gene via multiple pathways

Abstract Members of the enhancer of split- and hairy-related protein (SHARP) family, SHARP-1 and SHARP-2, are basic helix−loop−helix transcriptional repressors and belong to the clock genes. In this study, an effect of retinoic acid (RA) on the SHARP family gene expression in the differentiated cell...

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Published in:Journal of biochemistry (Tokyo) Vol. 170; no. 3; pp. 427 - 434
Main Authors: Hayashi, Momoko, Misaki, Toshinori, Yoshida, Sena, Tokutake, Hiroshi, Aruga, Tomoki, Yoda, Kazuya, Kenmochi, Eri, Saito, Kaho, Togashi, Momo, Nakano, Mai, Maejima, Misato, Amemiya, Riho, Sakuma, Airi, Nakazawa, Yuuri, Takagi, Katsuhiro, Tsukada, Akiko, Yamada, Kazuya
Format: Journal Article
Language:English
Published: England Oxford University Press 01-09-2021
Subjects:
hepatic H4IIE cells
signaling pathway
gene transcription
retinoic acid
SHARP-2
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Summary:Abstract Members of the enhancer of split- and hairy-related protein (SHARP) family, SHARP-1 and SHARP-2, are basic helix−loop−helix transcriptional repressors and belong to the clock genes. In this study, an effect of retinoic acid (RA) on the SHARP family gene expression in the differentiated cells was examined. RA rapidly and temporarily induced the SHARP-2 mRNA expression in hepatic H4IIE cells. Then, whether the SHARP-2 mRNA expression is altered by dexamethasone (Dex), insulin, and the combination of RA and Dex or RA and insulin was examined. Dex had different effects on the expression of SHARP-2 mRNA in the presence or absence of RA. Then, the molecular mechanisms were investigated using inhibitors of various signaling molecules. The RA-induction of SHARP-2 mRNA level was mainly inhibited by LY294002, staurosporine, and actinomycin D, respectively. Finally, whether RA acts on the transcriptional regulatory region of the SHARP-2 gene was analysed using luciferase reporter gene assay. At least two RA-responsive regions were mapped at the nucleotide sequences between −3,700 and −1,600 of the SHARP-2 gene. In addition, this effect was dependent on the RA receptor and retinoid X receptor. Thus, we conclude that RA stimulated transcription of the SHARP-2 gene via multiple pathways. Graphical Abstract
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ISSN:0021-924X
1756-2651
DOI:10.1093/jb/mvab058