A CHAF1B-Dependent Molecular Switch in Hematopoiesis and Leukemia Pathogenesis. Cancer Cell 2018 Nov 12;34(5):707-723.e7
Date
11/14/2018Pubmed ID
30423293Pubmed Central ID
PMC6235627DOI
10.1016/j.ccell.2018.10.004Scopus ID
2-s2.0-85055279677 (requires institutional sign-in at Scopus site) 52 CitationsAbstract
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.
Author List
Volk A, Liang K, Suraneni P, Li X, Zhao J, Bulic M, Marshall S, Pulakanti K, Malinge S, Taub J, Ge Y, Rao S, Bartom E, Shilatifard A, Crispino JDAuthor
Sridhar Rao MD, PhD Associate Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAnimals
Binding Sites
CCAAT-Enhancer-Binding Proteins
Cell Differentiation
Cell Line, Tumor
Cell Proliferation
Chromatin
Chromatin Assembly Factor-1
Exoribonucleases
Female
Hematopoiesis
Humans
Jurkat Cells
Leukemia, Myeloid, Acute
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Nucleosomes
Protein Binding
Proteins
Repressor Proteins
Ribonucleases
