Diagenode

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


Jung J, Buisman SC, Weersing E, Dethmers-Ausema A, Zwart E, Schepers H, Dekker MR, Lazare SS, Hammerl F, Skokova Y, Kooistra SM, Klauke K, Poot RA, Bystrykh LV, de Haan G

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.

Tags
Antibody
Microplex Library Preparation kit

Share this article

Published
February, 2019

Source

Products used in this publication

  • cut and tag antibody icon
    C15410193
    H3K9me3 Antibody
  • ChIP kit icon
    C05010012
    MicroPlex Library Preparation Kit v2 (12 indexes)

Events

  • AACR 2024
    San Diego, California, USA
    Apr 5-Apr 10, 2024
 See all events

News

 See all news


The European Regional Development Fund and Wallonia are investing in your future.

Extension of industrial buildings and new laboratories.


       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy   |   Diagenode Diagnostics