Inhibitors of Histone Deacetylase Down-regulate the Expression of Steroidogenic Factor 1 in Adrenocorticol Cells
Date Issued
2005
Date
2005
Author(s)
lai, Cheng-Fen
DOI
en-US
Abstract
The orphan nuclear receptor steroidogenic factor 1 (SF-1, A4BP, or NR5A1) is a key transcription factor that regulates the expression of many steroidogenic enzymes. It has also been demonstrated to play an important role in the development and differentiation of hypothalamus, pituitary, adrenal glands, and gonads. Being such an important factor, the regulation of SF-1 expression is highly investigated. We used inhibitors of histone deacetylases which generally activate gene expression and used as anticancer drugs such as trichostatin A and sodium butyrate. Histone deacetylase inhibitors although increased the acetylation of Histone 4, reduced the protein content of SF1 and cytochrome P450 side-chain cleavage enzyme, a SF-1 controlled gene, in a dose and time-dependent manner in adrenocorticol cells, Y1 and H295 cells. In a reporter assay, TSA reduced the SF-1 promoter activity. In Y1 stable clone, which expresses SF-1-HA driven by CMV promoter, TSA increased exogenous SF-1-HA protein, however, reduced endogenous SF-1 protein. Both results indicate that SF-1 is transcriptionally down-regulated by these inhibitors. TSA reduced binding of E-box and CCAAT box binding factor to SF-1 promoter in Electorphoretic Mobility Shift Assay. The E-box binding proteins, USF1 (upstream stimulatory factor 1) and USF2 were down-regulated by TSA as well as SF-1. These results suggest that TSA-inhibited expression of SF-1 may provide insight to uncover the regulatory mechanism of SF-1 gene. Interesting, we found that TSA treatment increases mRNA of SCC and USF2 but reduces USF1 mRNA in Quantitative-Real-Time PCR. Increased USF1 mRNA and reduced USF1 protein content after TSA treatment provides a new association of protein stability and acetylation.
Subjects
類
固醇轉錄
因子
孤核受體
腎上腺皮質腫瘤細胞
組蛋白去乙醯基轉移酵素抑制劑
乙醯化
膽固醇側鏈分切酵素
上游刺激因子一及二
histone acetylatransferase
P450 side chain cleavage enzyme
the cholesterol side-chain cleavage enzyme
steroidogenic factor 1
trichostatin A
SDGs
Type
thesis
File(s)![Thumbnail Image]()
Loading...
Name
ntu-94-R92629015-1.pdf
Size
23.31 KB
Format
Adobe PDF
Checksum
(MD5):a73f7600219f1d4224ade28f21ebc0fb