A CHAF1B-Dependent Molecular Switch in Hematopoiesis and Leukemia Pathogenesis

Andrew Volk, Kaiwei Liang, Praveen Suraneni, Xinyu Li, Jianyun Zhao, Marinka Bulic, Stacy Marshall, Kirthi Pulakanti, Sebastien Malinge, Jeffrey Taub, Yubin Ge, Sridhar Rao, Elizabeth Bartom, Ali Shilatifard, John D. Crispino*

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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. Volk et al. show that overexpression of the chromatin assembly factor complex subunit CHAF1B promotes leukemogenesis by interfering with chromatin occupancy of transcription factors that promote myeloid differentiation. Reducing CHAF1B activity suppresses leukemogenesis without impairing normal hematopoiesis.

Original languageEnglish (US)
Pages (from-to)707-723.e7
JournalCancer Cell
Volume34
Issue number5
DOIs
StatePublished - Nov 12 2018

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Keywords

  • CAF1
  • CHAF1B
  • MLL-AF9
  • hematopoiesis

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

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, J. D. (2018). A CHAF1B-Dependent Molecular Switch in Hematopoiesis and Leukemia Pathogenesis. Cancer Cell, 34(5), 707-723.e7. https://doi.org/10.1016/j.ccell.2018.10.004