DNA Methylation of Intragenic Cpg Islands Depends on Their Transcriptional Activity During Differentiation and Disease
DNA methylation of intragenic CpG islands depends on their transcriptional activity during differentiation and disease Danuta M. Jeziorskaa, Robert J. S. Murrayb,c,1, Marco De Gobbia,2, Ricarda Gaentzscha,3, David Garricka,4, Helena Ayyuba, Taiping Chend,EnLie, Jelena Teleniusa, Magnus Lyncha,5, Bryony Grahama, Andrew J. H. Smitha,f, Jonathan N. Lundc, Jim R. Hughesa, Douglas R. Higgsa,6, and Cristina Tufarellic,6 aMedical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford OX3 9DS, United Kingdom; bDepartment of Genetics, University of Leicester, Leicester LE1 7RH, United Kingdom; cDivision of Medical Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham, Royal Derby Hospital, Derby DE22 3DT, United Kingdom; dDepartment of Epigenetics and Molecular Carcinogenesis, Division of Basic Science Research, The University of Texas M. D. Anderson Cancer Center, Smithville, TX 78957; eChina Novartis Institutes for BioMedical Research, Shanghai 201203, China; and fMedical Research Council Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh EH16 4UU, United Kingdom Edited by Adrian P. Bird, University of Edinburgh, Edinburgh, United Kingdom, and approved July 28, 2017 (received for review February 23, 2017) The human genome contains ∼30,000 CpG islands (CGIs). While CGIs (RHBDF1), which becomes methylated during normal devel- associated with promoters nearly always remain unmethylated, many opment in vivo (11) (Fig. 1). of the ∼9,000 CGIs lying within gene bodies become methylated during In both cases, we show that methylation of these specific CGIs development and differentiation. Both promoter and intragenic CGIs is associated with transcription traversing the CGI, a reduction of may also become abnormally methylated as a result of genome rear- H3K4me3, a gain of H3K36me3, and DNA methyltransferase 3B rangements and in malignancy.
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