Low-level expression of human ACAT2 gene in monocytic cells is regulated by the C/EBP transcription factors.
Acyl-coenzyme A:cholesterol acyltransferases (ACATs) are the exclusive intracellular enzymes that catalyze the formation of cholesteryl/steryl esters (CE/SE). In our previous work, we found that the high-level expression of human ACAT2 gene with the CpG hypomethylation of its whole promoter was synergistically regulated by two transcription factors Cdx2 and HNF1α in the intestine and fetal liver. Here, we first observed that the specific CpG-hypomethylated promoter was correlated with the low expression of human ACAT2 gene in monocytic cell line THP-1. Then, two CCAAT/enhancer binding protein (C/EBP) elements within the activation domain in the specific CpG-hypomethylation promoter region were identified, and the expression of ACAT2 in THP-1 cells was evidently decreased when the C/EBP transcription factors were knock-downed using RNAi technology. Furthermore, ChIP assay confirmed that C/EBPs directly bind to their elements for low-level expression of human ACAT2 gene in THP-1 cells. Significantly, the increased expressions of ACAT2 and C/EBPs were also found in macrophages differentiated from both ATRA-treated THP-1 cells and cultured human blood monocytes. These results demonstrate that the low-level expression of human ACAT2 gene with specific CpG-hypomethylated promoter is regulated by the C/EBP transcription factors in monocytic cells, and imply that the lowly expressed ACAT2 catalyzes the synthesis of certain CE/SE that are assembled into lipoproteins for the secretion.
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Dongqing
D
Guo
Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
Ming
M
Lu
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Xihan
X
Hu
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Jiajia
J
Xu
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Guangjing
G
Hu
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Ming
M
Zhu
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Xiaowei
X
Zhang
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Qin
Q
Li
Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
Catherine C Y
CC
Chang
Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
Tayuan
T
Chang
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.|College of Life Sciences, The Institute for Advanced Studies, Wuhan University, Wuhan 430072, China.
Baoliang
B
Song
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Ying
Y
Xiong
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China blli@sibcb.ac.cn.
Boliang
B
Li
D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation; D002460:Cell Line; D018899:CpG Islands; D019175:DNA Methylation; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000166:cytology; D009000:Monocytes / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D002785:Sterol O-Acyltransferase / Q000235:genetics*; D000097587:Sterol O-Acyltransferase 2
D022762:CCAAT-Enhancer-Binding Proteins; D002785:Sterol O-Acyltransferase; D000097587:Sterol O-Acyltransferase 2
ACAT2 expression; C/EBP; cis element; monocytic cell; promoter-CpG methylation
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