Genome-wide maps of chromatin state in Ba/F3 cell with PAX5-KIDINS220 fusion protein

PAX5-KIDINS220 (PAX5-K220) is a novel chimeric fusion gene identified in a pediatric Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL) patient, but the function of the encoded fusion protein has not yet been analyzed. Here, using in vitro murine assays and ChIP-sequencing, we demonstrate that PAX5-K220 is a nuclear protein that inhibits PAX5 transcriptional activity in a dominant-negative fashion, resulting in a B-cell differentiation block. Gene expression analysis and ChIP-sequencing revealed that PAX5-K220 is associated with multiple pathways related to chemotaxis and migration. Overall design: Examination of histone modification (H3K4me2) in Ba/F3 cell (murine pro-B cell)PAX5-KIDINS220（PAX5-K220）是在1例儿童费城染色体（Ph）样急性淋巴细胞白血病（ALL）患者中鉴定得到的新型嵌合融合基因，但其编码的融合蛋白功能尚未得到解析。本研究通过体外小鼠实验与染色质免疫沉淀测序（ChIP-sequencing）证实，PAX5-K220为核蛋白，可通过显性负调控方式抑制PAX5的转录活性，进而引发B细胞分化阻滞。基因表达分析与染色质免疫沉淀测序结果显示，PAX5-K220与多个趋化性及迁移相关通路存在关联。实验整体设计：对Ba/F3细胞（小鼠前B细胞）中的组蛋白修饰H3K4me2进行检测。