Putnik Milica, Brodin David, Wojdacz Tomasz K, Fagerström-Billai Fredrik, Dahlman-Wright Karin, Wallberg Annika E
Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, 171 77, Stockholm, Sweden.
Bioinformatics and Expression Core Facility (BEA), Karolinska Institutet, Hälsovägen 7-9, 141 83, Huddinge, Sweden.
Mol Biol Rep. 2016 Mar;43(3):141-50. doi: 10.1007/s11033-016-3946-6. Epub 2016 Feb 8.
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.
类主谋蛋白1(MAML1)是一种转录共调节因子,与许多系统(如神经、肌肉和泌尿生殖系统)的早期发育有关。本研究旨在探讨MAML1对人胚肾细胞DNA甲基化和RNA表达的全基因组效应。使用Illumina Infinium HumanMethylation450 BeadChip芯片、甲基化敏感的高分辨率熔解技术、芯片分析甲基化流程和RNA分析方法来研究MAML1对表观基因组的影响。我们发现,在表达MAML1的细胞中,有11802个CpG位点存在差异甲基化,而只有225个基因存在差异表达。MAML1过表达诱导的全基因组差异高甲基化多于低甲基化变化。此外,差异甲基化区域主要定位于3'非翻译区、基因内区域和基因体,在较小程度上定位于基因调控序列。基因本体分析表明,差异变化的基因(包括HOXC11、HTATIP2、SLFN12和SOX11)参与泌尿生殖系统发育、细胞黏附和胚胎发生的调控。本研究是首份展示单个共调节因子对DNA甲基化和基因表达的全基因组效应的报告。我们的结果强调并支持转录共调节因子对细胞甲基化组的作用。