Diagenode

>>>   Click for Diagenode’s approach to COVID-19

Genomic deregulation of PRMT5 supports growth and stress tolerance in chronic lymphocytic leukemia.


Schnormeier AK, Pommerenke C, Kaufmann M, Drexler HG, Koeppel M

Patients suffering from chronic lymphocytic leukemia (CLL) display highly diverse clinical courses ranging from indolent cases to aggressive disease, with genetic and epigenetic features resembling this diversity. Here, we developed a comprehensive approach combining a variety of molecular and clinical data to pinpoint translocation events disrupting long-range chromatin interactions and causing cancer-relevant transcriptional deregulation. Thereby, we discovered a B cell specific cis-regulatory element restricting the expression of genes in the associated locus, including PRMT5 and DAD1, two factors with oncogenic potential. Experimental PRMT5 inhibition identified transcriptional programs similar to those in patients with differences in PRMT5 abundance, especially MYC-driven and stress response pathways. In turn, such inhibition impairs factors involved in DNA repair, sensitizing cells for apoptosis. Moreover, we show that artificial deletion of the regulatory element from its endogenous context resulted in upregulation of corresponding genes, including PRMT5. Furthermore, such disruption renders PRMT5 transcription vulnerable to additional stimuli and subsequently alters the expression of downstream PRMT5 targets. These studies provide a mechanism of PRMT5 deregulation in CLL and the molecular dependencies identified might have therapeutic implementations.

Tags
Antibody

Share this article

Published
June, 2020

Source

Products used in this publication

  • Antibody ChIP-seq grade icon
    C15410196
    H3K27ac Antibody - ChIP-seq Grade
  • Antibody ChIP-seq grade icon
    C15410195
    H3K27me3 Antibody - ChIP-seq Grade
  • Antibody ChIP-seq grade icon
    C15410003-50
    H3K4me3 Antibody - ChIP-seq Grade

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