Low-level expression of human ACA T2 gene in monocytic cells is regulated by the C/EBP transcription factors

• Published in: 生物化学与生物物理学报：英文版 Vol. 48; no. 11; pp. 980 - 989
• Main Author: Dongqing Guo Ming Lu Xihan Hu Jiaiia Xu Guangjing Hu Ming Zhu Xiaowei Zhang Qin Li Catherine C. Y. Chang Tayuan Chang Baoliang Song Ying Xiong Boliang Li
• Format: Journal Article
• Language: English
• Published: 2016
• ISSN: 1672-9145; 1745-7270

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 HNFlcc 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-I. 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 expres- sion 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 cul- tured 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 cer- tain CE/SE that are assembled into lipoproteins for the secretion.