Hepatocyte nuclear factor-4α plays pivotal roles in the regulation of mouse carboxylesterase 2 gene transcription in mouse liver
Section snippets
Cell cultures, total RNA isolation, cDNA synthesis, and reverse transcription-polymerase chain reaction (RT-PCR) analysis
HepG2 cells, human hepatoma cells, were obtained from the Institute of Development, Aging and Cancer, Tohoku University (Sendai, Japan). HepG2 cells were maintained at 37 °C with 5% CO2 in Dulbecco’s modified Eagle’s medium (D-MEM) (Invitrogen, Carlsbad, CA) supplemented with 10% (v/v) heat-inactivated fetal bovine serum (FBS) and 50 U/mL penicillin and with 50 μg/mL streptomycin. FLC7 cells [18], human hepatoma cells, were kindly provided by Dr. Seishi Nagamori (Kyorin University, Tokyo, Japan)
Enhancement of promoter activity of the mCES2 gene by expression of HNF-4α
This study was begun by searching for a DR1 element by using a searching program for transcription factor binding sites (Match™, http://www.gene-regulation.com/). As shown in Fig. 1A, the putative DR1 element was found to be close to a transcription start site, and the nucleotide sequence was very similar to those of DR1 elements in the human transthyretin gene and the human apolipoprotein C III gene to which it has been reported that HNF-4α could bind [5]. Next, we performed luciferase assays
Discussion
The results obtained in the first part of this study verified our initial hypothesis that HNF-4α is directly involved in mCES2 gene transcription, and the results obtained in the second part of this study showed that a nuclear receptor cascade triggered by bile acids signal can affect mCES2 mRNA expression. To the best of our knowledge, this is the first report presenting results that show the involvement of nuclear receptors in the transcription of CES genes.
Several HNF-4α isoforms are known,
Acknowledgments
This work was supported in part by a Grant (14572090) from the Ministry of Education, Sciences, Sports, and Culture of Japan. We thank Dr. Seishi Nagamori for providing FLC7 cells.
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