Diagenode

Global distribution of DNA hydroxymethylation and DNA methylation in chronic lymphocytic leukemia.


Wernig-Zorc S, Yadav MP, Kopparapu PK, Bemark M, Kristjansdottir HL, Andersson PO, Kanduri C, Kanduri M

BACKGROUND: Chronic lymphocytic leukemia (CLL) has been a good model system to understand the functional role of 5-methylcytosine (5-mC) in cancer progression. More recently, an oxidized form of 5-mC, 5-hydroxymethylcytosine (5-hmC) has gained lot of attention as a regulatory epigenetic modification with prognostic and diagnostic implications for several cancers. However, there is no global study exploring the role of 5-hydroxymethylcytosine (5-hmC) levels in CLL. Herein, using mass spectrometry and hMeDIP-sequencing, we analysed the dynamics of 5-hmC during B cell maturation and CLL pathogenesis. RESULTS: We show that naïve B-cells had higher levels of 5-hmC and 5-mC compared to non-class switched and class-switched memory B-cells. We found a significant decrease in global 5-mC levels in CLL patients (n = 15) compared to naïve and memory B cells, with no changes detected between the CLL prognostic groups. On the other hand, global 5-hmC levels of CLL patients were similar to memory B cells and reduced compared to naïve B cells. Interestingly, 5-hmC levels were increased at regulatory regions such as gene-body, CpG island shores and shelves and 5-hmC distribution over the gene-body positively correlated with degree of transcriptional activity. Importantly, CLL samples showed aberrant 5-hmC and 5-mC pattern over gene-body compared to well-defined patterns in normal B-cells. Integrated analysis of 5-hmC and RNA-sequencing from CLL datasets identified three novel oncogenic drivers that could have potential roles in CLL development and progression. CONCLUSIONS: Thus, our study suggests that the global loss of 5-hmC, accompanied by its significant increase at the gene regulatory regions, constitute a novel hallmark of CLL pathogenesis. Our combined analysis of 5-mC and 5-hmC sequencing provided insights into the potential role of 5-hmC in modulating gene expression changes during CLL pathogenesis.

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Published
January, 2019

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Products used in this publication

  • RFX5-polyclonal-antibody-diagenode
    C15200081-100
    5-methylcytosine (5-mC) monoclonal antibody 33D...
  • RFX5-polyclonal-antibody-diagenode
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    5-hydroxymethylcytosine (5-hmC) monoclonal anti...
  • Antibody ChIP-seq grade icon
    C15410174
    H3K27ac polyclonal antibody - Classic
  • Antibody ChIP-seq grade icon
    C15410037-50
    H3K4me1 polyclonal antibody - Classic
  • ChIP kit icon
    C01010080
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  • Methylation kit icon
    C02010030
    hMeDIP kit x16 (monoclonal rat antibody)
  • MagMeDIP qPCR Kit box
    C02010021
    MagMeDIP kit

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