Lysine-specific Demethylase 1 Represses THP-1 Monocyte-to-macrophage Differentiation  

作　　者：Rui-feng Yang Guo-wei Zhao Shu-ting Liang Hou-zao Chen De-pei Liu 

机构地区：[1]National Laboratory of Medical Molecular Biology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences & Peking Union Medical College

出　　处：《Chinese Medical Sciences Journal》2013年第2期82-87,共6页中国医学科学杂志（英文版）

基　　金：Supported by National Natural Science Foundation of China(31271227,30721063,81161120551);National Basic Research Program of China(973 Program,2011CB503902,2011CB965203)

摘　　要：Objective To investigate the role of lysine-specific demethylase 1 （LSD1） in the process of THP-1 monocyte-to-macrophage differentiation. Methods Quantitative reverse transcription-polymerase chain reaction （qRT-PCR） and Western blotting were performed to analyze the expression of LSD1 and interleukin-6 （IL-6） in THP-1 monocytes and THP-l-derived macrophages. Chromatin immunoprecipitation （ChiP） assay was applied to detect the occupancy of LSD1 and H3K4 methylation at IL-6 promoter during THP-1 monocyte-to-macrophage differentiation. IL-6 mRNA level and H3K4 methylation at IL-6 promoter were analyzed using qRT-PCR and ChiP assay in LSD 1 -knockdown THP- 1 cells treated with 12-O-tetradecanoylphorbol- 13-acetate （TPA） for 0 4, 8, 12, and 24 hours. Fluorescence activated flow cytometry was performed to reveal the percentage of macrophages differentiated from THP- 1 monocytes. Results The expression of LSD1 reduced during THP-1 monocyte-to-macrophage differentiation （P〈0.01）. LSD1 occupancy decreased and H3K4 methylation increased at IL-6 promoter during the differentiation. With knockdown of LSD1, H3K4 methylation at IL-6 promoter was found increased after TPA treatment at different times points （all P〈0.05, except 24 hours）. The percentage of macrophages increased significantly in theTHP-I cells with LSD1 knockdown （P〈0.05）. Conclusions LSD1 is repressed during the monocyte-to-macrophage differentiation of THP-1 cells. Suppression of LSD 1-mediated H3K4 demethylation may be required for THP-1 monocyte-to-macrophage differentiation.

关 键 词：lysine-specific demethylase 1 INTERLEUKIN-6 H3K4 methylation monocyte-to-macrophage differentiation 

分 类 号：R341[医药卫生—基础医学]