title: The transcriptional coregulator MAML1 affects DNA methylation and gene expression patterns in human embryonic kidney cells.
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.
authors: Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, 171 77, Stockholm, Sweden.
authors: Milica
authors: M
authors: Putnik
authors: Bioinformatics and Expression Core Facility (BEA), Karolinska Institutet, Hälsovägen 7-9, 141 83, Huddinge, Sweden.
authors: David
authors: D
authors: Brodin
authors: Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, 171 77, Stockholm, Sweden.
authors: Tomasz K
authors: TK
authors: Wojdacz
authors: Bioinformatics and Expression Core Facility (BEA), Karolinska Institutet, Hälsovägen 7-9, 141 83, Huddinge, Sweden.
authors: Fredrik
authors: F
authors: Fagerström-Billai
authors: Bioinformatics and Expression Core Facility (BEA), Karolinska Institutet, Hälsovägen 7-9, 141 83, Huddinge, Sweden.
authors: Karin
authors: K
authors: Dahlman-Wright
authors: Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, 171 77, Stockholm, Sweden. annika.wallberg@ki.se.
authors: Annika E
authors: AE
authors: Wallberg
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger; D055751:SOXC Transcription Factors / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; C484731:HOXC11 protein, human; D018398:Homeodomain Proteins; C430872:MAML1 protein, human; D012333:RNA, Messenger; C097473:SOX11 protein, human; D055751:SOXC Transcription Factors; D014157:Transcription Factors; D000123:Acetyltransferases; C111246:HTATIP2 protein, human
keywords: DNA methylation; Gene expression; HEK293; MAML1; MS-HRM; Real-Time PCR