Inhibitors of LSD1 target demethylase-independent activity to induce differentiation in acute myeloid leukemia [ChIP-Seq: histone modifications]

To determine whether changes in histone modifications directly correlate with changes in transcription, THP1 AML cells were treated with a potent and selective LSD1 inhibitor (OG86) and then subjected to concomitant RNA sequencing (RNAseq) and ChIP sequencing (ChIPseq) for monomethyl-, dimethyl- and trimethyl histone H3 modifications. Overall design: THP1 AML cells were treated with 250nM OG86 or DMSO vehicle for 24 hours in semi-solid culture.

为探究组蛋白修饰的变化是否与转录变化存在直接相关性，研究人员采用强效且高选择性的赖氨酸特异性去甲基化酶1（Lysine-specific demethylase 1, LSD1）抑制剂OG86处理THP1急性髓系白血病（Acute Myeloid Leukemia, AML）细胞，随后对其开展同步的RNA测序（RNA sequencing, RNAseq）以及针对组蛋白H3单甲基化、二甲基化与三甲基化修饰的染色质免疫沉淀测序（Chromatin Immunoprecipitation sequencing, ChIPseq）。实验整体设计：将THP1 AML细胞置于半固体培养基中，以250nM浓度的OG86或二甲基亚砜（DMSO）对照溶剂处理24小时。