2018年2月1日
A candidate functional SNP rs7074440 in TCF7L2 alters gene expression through C-FOS in hepatocytes
FEBS Letters
- 巻
- 592
- 号
- 3
- 開始ページ
- 422
- 終了ページ
- 433
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1002/1873-3468.12975
- 出版者・発行元
- Wiley Blackwell
The SNP rs7903146 at the transcription factor 7-like 2 (TCF7L2) locus is established as the strongest known genetic marker for type 2 diabetes via genome-wide association studies. However, the functional SNPs regulating TCF7L2 expression remain unclear. Here, we show that the SNP rs7074440 is a candidate functional SNP highly linked with rs7903146. A reporter plasmid with rs7074440 normal allele sequence exhibited 15-fold higher luciferase activity compared with risk allele sequence in hepatocytes, demonstrating a strong enhancer activity at rs7074440. Additionally, we identified C-FOS as an activator binding to the rs7074440 enhancer using a TFEL genome-wide screen method. Consistently, knockdown of C-FOS significantly reduced TCF7L2 expression in hepatocytes. Collectively, a novel enhancer regulating TCF7L2 expression was revealed through searching for functional SNPs.
- ID情報
-
- DOI : 10.1002/1873-3468.12975
- ISSN : 1873-3468
- ISSN : 0014-5793
- PubMed ID : 29331016
- SCOPUS ID : 85040778196