I. An emerging realm of biological regulation: RNA epigenetics. Distribution and function of RNA hydroxymethylation.
When considering epigenetics, histone and DNA modifications took first place and high interest in biological and medical research. However, the emerging discoveries of RNA modifications is completely changing our views about epigenetics. Indeed, more than 100 types of chemical modifications of RNA have been identified in organism of all kingdoms of life. Understanding the scope and mechanisms of these dynamic RNA modifications, which is termed 'RNA epigenetics', is an area of current intense research and is currently a main research focus of our lab.
We have recently addressed the distribution, function and biology of a novel modification of RNA (Delatte et al. Science. 2016). Our work opened new research prospects in an emerging realm of biological regulation: RNA epigenetics.
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II: Mechanisms of DNA methylation and hydroxymethylation and their dysregulations in cancers.
In the last years, we have tried to address the following 2 questions:
(i) Mechanisms of DNA methylation: we investigated the mechanisms by which genes silenced by DNA methylation and how are DNA methyltransferases (DNMT) targeted to specific genomic regions.
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We also identified several mechanisms by which DNMT activity, and thereby methylation of DNA, can be modulated. These studies shed new light on how posttranslational modifications might contribute to shaping the genomic CpG methylation landscape. Main Publication:
(ii) Role of TET and DNA hydroxymethylation: Our lab has been interested to the study of TET enzymes and another DNA modification, termed hydroxymethylation (5hmC). In 2009, findings of hmC as a novel epigenetic mark, which can act as an intermediate in DNA demethylation and is established by TET proteins, generated substantial excitement in the epigenetic field. It has been shown that members of the TET family (TET1, TET2, TET3) play a role in both physiological and pathological processes including embryonic stem (ES) cells maintenance, inner cell mass specification and hematological malignancies. We aimed to better understand the mechanisms by which TET/hmC are dysregulated in cancers.
III: Cancer epigenomics: the use of Next-Generation Sequencing (NGS) technologies
Besides studying fundamental mechanisms of DNA modifications as summarized above, our lab has developed a growing interest in cancer epigenomics. In this respect, as mentioned above, our lab is heading the Next-Generation Sequencing core facility, dedicated to Epigenetics (EPICS : website : epics.ulb.be). Regarding DNA methylome analyses, we have great expertise in "Infinium Methylation" assays, including bioinfomatic analyses. In one of our study, we have assessed the contribution of DNA methylation in previously unappreciated sequence contexts in breast cancer. Similar studies are currenly performed to map genome-wide hydroxymethylation. We are also skilled in performing ChIP-Seq, RNA-Seq, ATAC-Seq, and their associated bioinformatics analyses.
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