biostudies-literatureVolk ARobert H. Lurie Comprehensive Cancer CenterSamuel Waxman Cancer Research FoundationNorthwestern UniversityNational Cancer InstituteAmerican Society of HematologyNCI NIH HHSNational Institutes of HealthNIH HHS707-723.e7https://www.ebi.ac.uk/biostudies/studies/S-EPMC6235627biostudies-literatureUnknown34(5)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.Cancer cellA CHAF1B-Dependent Molecular Switch in Hematopoiesis and Leukemia Pathogenesis.PMC6235627T32 CA080621S10 OD0119961S10OD011996-01R35 CA197569P30 CA060553CA060553R01 CA101774R50 CA221848Pulakanti KTaub JRao SShilatifard ASuraneni PBulic MCrispino JDBartom ELi XVolk AGe YLiang KMarshall SZhao JMalinge SfalseA CHAF1B-Dependent Molecular Switch in Hematopoiesis and Leukemia Pathogenesis.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.2018-01-01T00:00:00Z2018 Nov2024-02-15T02:06:22.347Z2020-10-29T12:24:09ZS-EPMC62356273042329310.1016/j.ccell.2018.10.004