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The transcriptional coregulator MAML1 affects DNA methylation and gene expression patterns in human embryonic kidney cells

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Abstract

Mastermind-like 1 (MAML1) is a transcriptional coregulator that has been associated with early development of many systems such as neuronal, muscular and urogenital. The present study aimed to explore the genome wide effects of MAML1 on DNA methylation and RNA expression in human embryonic kidney cells. Infinium HumanMethylation450 BeadChip Illumina array, methylation-sensitive high-resolution melt technique, Chip Analysis Methylation Pipeline and RNA profiling approaches were used to study MAML1 effects on the epigenome. We found that 11802 CpG sites were differentially methylated in MAML1-expressing cells while only 225 genes were differentially expressed. MAML1 overexpression induced more global differential hypermethylation than hypomethylation changes. In addition, the differentially methylated regions were mapped predominantly to 3′untranslated regions, intragenic regions and gene bodies and to a lesser extent to gene regulatory sequences. Gene ontology analysis revealed that the differentially changed genes (including HOXC11, HTATIP2, SLFN12 and SOX11) are involved in the regulation of urogenital system development, cell adhesion and embryogenesis. This study is the first report that shows the global effect of a single coregulator on DNA methylation and gene expression. Our results stress and support the effects of transcriptional coregulators on the cell methylome.

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Acknowledgments

This work was supported by a Grant from the Swedish Research Council to A.E.W.

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Authors and Affiliations

  1. Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, 171 77, Stockholm, Sweden

    Milica Putnik, Tomasz K. Wojdacz & Annika E. Wallberg

  2. Bioinformatics and Expression Core Facility (BEA), Karolinska Institutet, Hälsovägen 7-9, 141 83, Huddinge, Sweden

    David Brodin, Fredrik Fagerström-Billai & Karin Dahlman-Wright

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  1. Milica Putnik
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  2. David Brodin
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  3. Tomasz K. Wojdacz
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  4. Fredrik Fagerström-Billai
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  5. Karin Dahlman-Wright
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  6. Annika E. Wallberg
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Correspondence to Annika E. Wallberg.

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11033_2016_3946_MOESM1_ESM.pptx

Supplementary Fig. 1: Boxplots of differentially methylated probes, stratified by annotated genomic region. A. Distribution of all differentially methylated probes. B. Distribution of all differentially hypomethylated probes. C. Distribution of all differentially hypermethylated probes. The width of the boxplot reflects the number of observations in each category. UTR: untranslated region; TSS200: 200 bp within transcriptional start site; TSS1500: 1.5 kb within transcriptional start site; N shore: north shore (upstream from CpG island); N shelf: north shelf (upstream from north shore); S shore: south shore (downstream from CpG island); S shelf: south shelf (downstream from south shore). (PPTX 131 kb)

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Putnik, M., Brodin, D., Wojdacz, T.K. et al. The transcriptional coregulator MAML1 affects DNA methylation and gene expression patterns in human embryonic kidney cells. Mol Biol Rep 43, 141–150 (2016). https://doi.org/10.1007/s11033-016-3946-6

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  • DOI: https://doi.org/10.1007/s11033-016-3946-6

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