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Publication : A CHAF1B-Dependent Molecular Switch in Hematopoiesis and Leukemia Pathogenesis.

First Author  Volk A Year  2018
Journal  Cancer Cell Volume  34
Issue  5 Pages  707-723.e7
PubMed ID  30423293 Mgi Jnum  J:266848
Mgi Id  MGI:6256871 Doi  10.1016/j.ccell.2018.10.004
Citation  Volk A, et al. (2018) A CHAF1B-Dependent Molecular Switch in Hematopoiesis and Leukemia Pathogenesis. Cancer Cell 34(5):707-723.e7
abstractText  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.
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