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  • 1
    Publication Date: 2016-01-28
    Description: Hydroxymethylcytosine, well described in DNA, occurs also in RNA. Here, we show that hydroxymethylcytosine preferentially marks polyadenylated RNAs and is deposited by Tet in Drosophila. We map the transcriptome-wide hydroxymethylation landscape, revealing hydroxymethylcytosine in the transcripts of many genes, notably in coding sequences, and identify consensus sites for hydroxymethylation. We found that RNA hydroxymethylation can favor mRNA translation. Tet and hydroxymethylated RNA are found to be most abundant in the Drosophila brain, and Tet-deficient fruitflies suffer impaired brain development, accompanied by decreased RNA hydroxymethylation. This study highlights the distribution, localization, and function of cytosine hydroxymethylation and identifies central roles for this modification in Drosophila.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Delatte, Benjamin -- Wang, Fei -- Ngoc, Long Vo -- Collignon, Evelyne -- Bonvin, Elise -- Deplus, Rachel -- Calonne, Emilie -- Hassabi, Bouchra -- Putmans, Pascale -- Awe, Stephan -- Wetzel, Collin -- Kreher, Judith -- Soin, Romuald -- Creppe, Catherine -- Limbach, Patrick A -- Gueydan, Cyril -- Kruys, Veronique -- Brehm, Alexander -- Minakhina, Svetlana -- Defrance, Matthieu -- Steward, Ruth -- Fuks, Francois -- R01 GM089992/GM/NIGMS NIH HHS/ -- T32 CA117846/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2016 Jan 15;351(6270):282-5. doi: 10.1126/science.aac5253.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB Cancer Research Center (U-CRC), Universite Libre de Bruxelles (ULB), Brussels, Belgium. ; Waksman Institute, Department of Molecular Biology and Biochemistry, Cancer Institute of New Jersey, Rutgers University, Piscataway, NJ, USA. ; Laboratory of Molecular Biology of the Gene, Faculty of Sciences, Universite Libre de Bruxelles, Gosselies, Belgium. ; Institut fur Molekularbiologie und Tumorforschung, Philipps-Universitat Marburg, Marburg, Germany. ; Department of Chemistry, University of Cincinnati, Cincinnati, OH, USA. ; Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB Cancer Research Center (U-CRC), Universite Libre de Bruxelles (ULB), Brussels, Belgium. ffuks@ulb.ac.be.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26816380" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*abnormalities/metabolism ; Cell Line ; Cytosine/*analogs & derivatives/metabolism ; Dioxygenases/genetics/metabolism ; Drosophila melanogaster/genetics/*growth & development/metabolism ; Methylation ; RNA, Messenger/genetics/*metabolism ; Transcriptome
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2018-06-21
    Description: Ten-eleven translocation enzymes (TET1, TET2, and TET3), which induce DNA demethylation and gene regulation by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), are often down-regulated in cancer. We uncover, in basal-like breast cancer (BLBC), genome-wide 5hmC changes related to TET1 regulation. We further demonstrate that TET1 repression is associated with high expression of immune markers and high infiltration by immune cells. We identify in BLBC tissues an anticorrelation between TET1 expression and the major immunoregulator family nuclear factor B (NF-B). In vitro and in mice, TET1 is down-regulated in breast cancer cells upon NF-B activation through binding of p65 to its consensus sequence in the TET1 promoter. We lastly show that these findings extend to other cancer types, including melanoma, lung, and thyroid cancers. Together, our data suggest a novel mode of regulation for TET1 in cancer and highlight a new paradigm in which the immune system can influence cancer cell epigenetics.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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