Genome-wide analysis of H3K79 dimethylation in normal and MLL-AF4 leukemic pre-B cells. Mus musculus

We created a mouse model where conditional expression of physiologic levels of an Mll-AF4 fusion oncogene induces development of acute lymphoblastic (ALL) or acute myeloid leukemias (AML). ChIP-chip analysis demonstrated increased histone H3 Lysine 79 (H3K79) dimethylation that correlated with Mll-AF4 associated gene expression profiles in murine ALLs, and in human MLL-rearranged leukemias. In addition, human MLL-rearranged ALLs can be distinguished from other ALLs by their genome-wide H3K79 methylation profiles. Keywords: Cell type comparison Overall design: DNA was immunoprecipitated with anti-dimethyl-H3K79 antibodies from purified marrow preB cells of normal mice or animals made leukemic by activation of an MLL-AF4 fusion. The ChIP DNA was then hybridized to Affymetrix promoter tiling microarrays.

我们构建了一种小鼠模型，在该模型中，生理水平的Mll-AF4融合癌基因（Mll-AF4 fusion oncogene）的条件性表达可诱导急性淋巴细胞白血病（acute lymphoblastic leukemia, ALL）与急性髓系白血病（acute myeloid leukemia, AML）的发生。染色质免疫沉淀芯片（chromatin immunoprecipitation on chip, ChIP-chip）分析结果表明，在小鼠ALL以及人类MLL重排白血病样本中，组蛋白H3赖氨酸79二甲基化（histone H3 Lysine 79 dimethylation, H3K79）水平的升高与Mll-AF4相关的基因表达谱存在显著关联。此外，人类MLL重排型ALL可凭借其全基因组H3K79甲基化谱，与其他ALL亚型实现区分。
关键词：细胞类型比较
整体实验设计：从正常小鼠的纯化骨髓前B细胞（preB cell），以及经MLL-AF4融合基因激活诱导白血病的动物的纯化骨髓前B细胞中提取DNA，使用抗二甲基H3K79抗体进行免疫沉淀；随后将所得染色质免疫沉淀DNA与Affymetrix启动子平铺微阵列进行杂交。