CBX7 Induces Self-Renewal of Human Normal and Malignant Hematopoietic Stem and Progenitor Cells by Canonical and Non-canonical Interactions

Cell Rep. 2019 Feb 12;26(7):1906-1918.e8. doi: 10.1016/j.celrep.2019.01.050.


In this study, we demonstrate that, among all five CBX Polycomb proteins, only CBX7 possesses the ability to control self-renewal of human hematopoietic stem and progenitor cells (HSPCs). Xenotransplantation of CBX7-overexpressing HSPCs resulted in increased multi-lineage long-term engraftment and myelopoiesis. Gene expression and chromatin analyses revealed perturbations in genes involved in differentiation, DNA and chromatin maintenance, and cell cycle control. CBX7 is upregulated in acute myeloid leukemia (AML), and its genetic or pharmacological repression in AML cells inhibited proliferation and induced differentiation. Mass spectrometry analysis revealed several non-histone protein interactions between CBX7 and the H3K9 methyltransferases SETDB1, EHMT1, and EHMT2. These CBX7-binding proteins possess a trimethylated lysine peptide motif highly similar to the canonical CBX7 target H3K27me3. Depletion of SETDB1 in AML cells phenocopied repression of CBX7. We identify CBX7 as an important regulator of self-renewal and uncover non-canonical crosstalk between distinct pathways, revealing therapeutic opportunities for leukemia.

Keywords: CBX7; Polycomb; SETDB1; hematopoietic stem cells; leukemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Fetal Blood / cytology
  • Fetal Blood / metabolism
  • HEK293 Cells
  • HL-60 Cells
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism*
  • Heterografts
  • Histone-Lysine N-Methyltransferase / metabolism
  • Humans
  • K562 Cells
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Polycomb Repressive Complex 1 / biosynthesis
  • Polycomb Repressive Complex 1 / genetics
  • Polycomb Repressive Complex 1 / metabolism*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Transcription, Genetic


  • CBX7 protein, human
  • Cbx7 protein, mouse
  • Histone-Lysine N-Methyltransferase
  • SETDB1 protein, human
  • SETDB1 protein, mouse
  • Polycomb Repressive Complex 1