Diagenode

DNMT3B overexpression contributes to aberrant DNA methylation and MYC-driven tumor maintenance in T-ALL and Burkitt’s lymphoma


Poole et al.

Aberrant DNA methylation is a hallmark of cancer. However, our understanding of how tumor cell-specific DNA methylation patterns are established and maintained is limited. Here, we report that in T-cell acute lymphoblastic leukemia (T-ALL) and Burkitt’s lymphoma the MYC oncogene causes overexpression of DNA methyltransferase (DNMT) 1 and 3B, which contributes to tumor maintenance. By utilizing a tetracycline-regulated MYC transgene in a mouse T-ALL (EμSRα-tTA;tet-o- MYC) and human Burkitt’s lymphoma (P493-6) model, we demonstrated that DNMT1 and DNMT3B expression depend on high MYC levels, and that their transcription decreased upon MYC-inactivation. Chromatin immunoprecipitation indicated that MYC binds to the DNMT1 and DNMT3B promoters, implicating a direct transcriptional regulation. Hence, shRNA-mediated knock-down of endogenous MYC in human T-ALL and Burkitt’s lymphoma cell lines, downregulated DNMT3B expression. Knock-down and pharmacologic inhibition of DNMT3B in T-ALL reduced cell proliferation associated with genome-wide changes in DNA methylation, indicating a tumor promoter function during tumor maintenance. We provide novel evidence that MYC directly deregulates the expression of both de novo and maintenance DNMTs, showing that MYC controls DNA methylation in a genome-wide fashion. Our finding that a coordinated interplay between the components of the DNA methylating machinery contributes to MYC-driven tumor maintenance highlights the potential of specific DNMTs for targeted therapies.

Tags
Premium RRBS Kit
DNA Methylation Profiling (RRBS Service)

Share this article

Published
August, 2017

Source

Products used in this publication

  • default alt
    G02020000
    RRBS Service (Reduced Representation Bisulfite ...
  • Methylation kit icon
    C02030032
    Premium RRBS kit (24 rxns) - replaced by Premiu...
  • Methylation kit icon
    C02030033
    Premium RRBS kit (96 rxns) - replaced by Premiu...
  • Methylation kit icon
    C02030036
    Premium RRBS kit V2 RRBS for low DNA amounts ...
  • Methylation kit icon
    C02030037
    Premium RRBS kit V2 x96 RRBS for low DNA amoun...

Events

  • 64th ASH Annual Meeting and Exposition 2022
    New Orleans, Louisiana, USA
    Dec 10-Dec 13, 2022
 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