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

Autor: Wernig-Zorc, Sara, Yadav, Mukesh Pratap, Kopparapu, Pradeep Kumar, Bemark, Mats, Kristjansdottir, Hallgerdur Lind, Andersson, Per-Ola, Kanduri, Chandrasekhar, Kanduri, Meena
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Epigenetics & Chromatin, Vol 12, Iss 1, Pp 1-15 (2019)
Epigenetics & Chromatin
ISSN: 1756-8935
Popis: 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. Electronic supplementary material The online version of this article (10.1186/s13072-018-0252-7) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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