scholarly journals Human acyl-CoA:cholesterol acyltransferase 2 gene expression in intestinal Caco-2 cells and in hepatocellular carcinoma

2006 ◽  
Vol 394 (3) ◽  
pp. 617-626 ◽  
Author(s):  
Bao-Liang Song ◽  
Can-Hua Wang ◽  
Xiao-Min Yao ◽  
Li Yang ◽  
Wen-Jing Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transcription Factor ◽  
Molecular Mechanism ◽  
Luciferase Reporter ◽  
Hepatoma Cell Line ◽  
Cis Elements ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression ◽  
Cdx2 Expression

Humans express two ACAT (acyl-CoA:cholesterol acyltransferase) genes, ACAT1 and ACAT2. ACAT1 is ubiquitously expressed, whereas ACAT2 is primarily expressed in intestinal mucosa and plays an important role in intestinal cholesterol absorption. To investigate the molecular mechanism(s) responsible for the tissue-specific expression of ACAT2, we identified five cis-elements within the human ACAT2 promoter, four for the intestinal-specific transcription factor CDX2 (caudal type homeobox transcription factor 2), and one for the transcription factor HNF1α (hepatocyte nuclear factor 1α). Results of luciferase reporter and electrophoretic mobility shift assays show that CDX2 and HNF1α exert a synergistic effect, enhancing the ACAT2 promoter activity through binding to these cis-elements. In undifferentiated Caco-2 cells, the ACAT2 expression is increased when exogenous CDX2 and/or HNF1α are expressed by co-transfection. In differentiated Caco-2 cells, the ACAT2 expression significantly decreases when the endogenous CDX2 or HNF1α expression is suppressed by using RNAi (RNA interference) technology. The expression levels of CDX2, HNF1α, and ACAT2 are all greatly increased when the Caco-2 cells differentiate to become intestinal-like cells. These results provide a molecular mechanism for the tissue-specific expression of ACAT2 in intestine. In normal adult human liver, CDX2 expression is not detectable and the ACAT2 expression is very low. In the hepatoma cell line HepG2 the CDX2 expression is elevated, accounting for its elevated ACAT2 expression. A high percentage (seven of fourteen) of liver samples from patients affected with hepatocellular carcinoma exhibited elevated ACAT2 expression. Thus, the elevated ACAT2 expression may serve as a new biomarker for certain form(s) of hepatocellular carcinoma.

scholarly journals Activity and tissue-specific expression of the transcription factor NF-E1 multigene family.

1990 ◽  
Vol 4 (10) ◽  
pp. 1650-1662 ◽  
Author(s):  
M Yamamoto ◽  
L J Ko ◽  
M W Leonard ◽  
H Beug ◽  
S H Orkin ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Multigene Family ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression

Autoantibody response to Sui1 and its tissue-specific expression in hepatocellular carcinoma

Tumor Biology ◽  
2015 ◽  
Vol 37 (2) ◽  
pp. 2547-2553 ◽  
Author(s):  
Jian-Wei Zhou ◽  
Yuan Li ◽  
Li-Xia Yue ◽  
Cheng-Lin Luo ◽  
Yao Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression ◽  
Autoantibody Response

scholarly journals Epigenetics and expression of key genes associated with cardiac fibrosis: NLRP3, MMP2, MMP9, CCN2/CTGF, and AGT

2020 ◽  
Author(s):  
Sruti Chandra ◽  
Kenneth C. Ehrlich ◽  
Michelle Lacey ◽  
Carl Baribault ◽  
Melanie Ehrlich
Keyword(s):  
Extracellular Matrix ◽  
Transcription Factor ◽  
Cardiac Fibrosis ◽  
Transcription Factor Binding ◽  
Open Chromatin ◽  
Specific Expression ◽  
Tissue Specific ◽  
Factor Binding ◽  
Tissue Specific Expression ◽  
Super Enhancer

AbstractExcessive inflammatory signaling and pathological remodeling of the extracellular matrix are important contributors to cardiac fibrosis and involve major changes in gene expression. We examined the relationships between tissue-specific expression and the epigenetics of five genes involved in these pathways, NLRP3, MMP2, MMP9, CCN2/CTGF, and AGT. The proteins encoded by these genes play major fibrosis-related roles in inflammasome formation, degradation of extracellular matrix proteins and remodeling of the extracellular matrix and vasculature, autocrine regulation of fibrosis, or cell signaling. Our analyses showed that the first four of these genes had super-enhancers (unusually strong enhancer clusters) that correlate with their very high expression in monocytes, neutrophils, fibroblasts, or venous cells. Expression of the gene encoding miR-223, a micro-RNA that plays an important role in downregulating NLRP3 protein levels, is also probably driven by the super-enhancer in which it is embedded. Enhancer chromatin for all these genes was inside as well as outside the gene body. While AGT, which encodes precursors of angiotensin II, lacked a super-enhancer, its tissue-specific expression profile correlates with the tissue-specific enhancer chromatin extending into its distant silent gene neighbor (CAPN9). Tissue-specific peaks of DNA hypomethylation, open chromatin (DNaseI hypersensitivity), and transcription factor binding were detected in subregions of these super-enhancers/enhancers that are likely to be the main drivers of expression of their associated gene. We found that CCN2/CTGF is co-expressed with its far-upstream neighbor LINC01013, a noncoding RNA gene, specifically in vein endothelial cells (HUVEC) and chondrocytes. Evidence from chromatin looping profiling (Hi-C) suggests coregulation of these genes in HUVEC. Our findings indicate the importance of understanding the often-overlooked roles of enhancers and their hypomethylated, transcription factor-binding subregions in the regulation of expression of fibrosis-related genes in normal and fibrotic tissue.

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