HOXA9 forms a repressive complex with nuclear matrix-associated protein SAFB to maintain acute myeloid leukemia [CUT&RUN/ChIP-Seq]. HOXA9 forms a repressive complex with nuclear matrix-associated protein SAFB to maintain acute myeloid leukemia [CUT&RUN/ChIP-Seq]

This study identifies HOXA9 protein interactome in acute myeloid leukemia cells. Integrated genomic, transcriptomic and proteomic analyses further demonstrated that the HOXA9-SAFB-chromatin complex associates with NuRD and HP1γ to repress the expression of factors associated with differentiation and apoptosis in leukemia maintenance. Overall design: Fusion oncoprotein MLL-AF9 positive acute myeloid leukemia cell line MOLM13 and primary AML cells are used for all the genomics experiments. Genome-wide binding of 5 chromatin factors (HOXA9, SAFB, MTA2, GATAD2A. HP1g) and 3 histone H3 modifications (H3K27me3, H3K9me2, H3K9me3) were investigated using CUT&RUN approach in MOLM13 cells. All experiments performed and sequenced in replicates.

本研究鉴定了急性髓系白血病（acute myeloid leukemia, AML）细胞中HOXA9蛋白的互作组（protein interactome）。整合基因组学、转录组学与蛋白质组学分析进一步证实，HOXA9-SAFB-染色质复合物可与NuRD复合物及HP1γ结合，从而抑制白血病维持过程中与分化及凋亡相关因子的表达。
实验设计概况：本研究所有基因组学实验均采用融合癌蛋白MLL-AF9阳性的急性髓系白血病细胞系MOLM13及原代AML细胞。在MOLM13细胞中，采用CUT&RUN技术对5种染色质因子（HOXA9、SAFB、MTA2、GATAD2A、HP1γ）及3种组蛋白H3修饰（H3K27me3、H3K9me2、H3K9me3）的全基因组结合情况进行了检测。所有实验均设置生物学重复并完成测序。