PRO-seq of 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 used precision nuclear run-on sequencing (PRO-seq) to define early transcriptional changes associated with INCB059872 treatment. Changes in nascent transcription could be traced back to a loss of CoREST activity resulting in activation of GFI1-regulated targets. Overall design: THP-1 cells were treated (in duplicate) with 25nM INCB059872 for 0, 6, 12, or 24hrs. PRO-seq was used to measure changes in nascent transcription.

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，目前正针对血液系统恶性肿瘤开展I期临床试验。本研究采用精准核运行测序（precision nuclear run-on sequencing, PRO-seq），以解析INCB059872处理相关的早期转录变化。新生转录水平的变化可追溯至核心抑制复合体（CoREST）活性丧失，进而介导生长因子独立1（GFI1）调控的靶基因激活。实验整体设计：将THP-1细胞以25nM浓度的INCB059872处理（设置两份生物学重复），处理时长分别为0、6、12或24小时；随后通过PRO-seq检测新生转录水平的变化。