ChIP-seq for histone acetylation and methylation in THP-1 cells treated with LSD1 inhibitor INCB059872

INCB059872 is a selective irreversible inhibitor of Lysine-Specific Demethylase 1 (LSD1) that is in phase 1 clinical trials in hematopoietic malignancies. We performed ChIP-seq for histone modifications to define the earliest regulatory events associated with INCB059872 treatment. Changes in acetylation were more dramatic than changes in methylation, and these changes could be traced back to a loss of CoREST activity at GFI1-regulated targets. Overall design: THP-1 cells were treated (in duplicate) with 25nM INCB059872 for 24 or 48 hours before crosslinking cells and performing ChIP-seq for H3K27ac or H3K4me1 and H3K4me2.

INCB059872是赖氨酸特异性去甲基化酶1（Lysine-Specific Demethylase 1, LSD1）的选择性不可逆抑制剂，目前正针对造血系统恶性肿瘤开展I期临床试验。本研究通过染色质免疫共沉淀测序（ChIP-seq）检测组蛋白修饰，以明确INCB059872处理相关的最早调控事件。结果显示，乙酰化水平的变化较甲基化更为显著，且此类变化可追溯至GFI1调控靶位点上CoREST活性的丧失。整体实验设计如下：将THP-1细胞以25nM浓度的INCB059872处理24或48小时（设置两份生物学重复），随后对细胞进行交联，并针对H3K27ac、H3K4me1及H3K4me2开展ChIP-seq检测。