Division of Hematology/Oncology, Northwestern University, 303 East Superior Street, 5-123, Chicago, IL 60611, USA.
Department of Biochemistry and Molecular Genetics, Northwestern University, Chicago, IL 60611, USA.
Cancer Cell. 2018 Nov 12;34(5):707-723.e7. doi: 10.1016/j.ccell.2018.10.004.
CHAF1B is the p60 subunit of the chromatin assembly factor (CAF1) complex, which is responsible for assembly of histones H3.1/H4 heterodimers at the replication fork during S phase. Here we report that CHAF1B is required for normal hematopoiesis while its overexpression promotes leukemia. CHAF1B has a pro-leukemia effect by binding chromatin at discrete sites and interfering with occupancy of transcription factors that promote myeloid differentiation, such as CEBPA. Reducing Chaf1b activity by either heterozygous deletion or overexpression of a CAF1 dominant negative allele is sufficient to suppress leukemogenesis in vivo without impairing normal hematopoiesis.
CHAF1B 是染色质组装因子（CAF1）复合物的 p60 亚基，它负责在 S 期的复制叉处组装组蛋白 H3.1/H4 异二聚体。在这里，我们报告 CHAF1B 是正常造血所必需的，而过表达则会促进白血病。CHAF1B 通过在离散位点结合染色质并干扰促进髓样分化的转录因子（如 CEBPA）的占据，从而发挥促白血病作用。通过杂合缺失或 CAF1 显性负等位基因的过表达降低 Chaf1b 的活性足以抑制体内白血病的发生，而不损害正常造血。
