title: Set7 mediated interactions regulate transcriptional networks in embryonic stem cells.
abstract: Histone methylation by lysine methyltransferase enzymes regulate the expression of genes implicated in lineage specificity and cellular differentiation. While it is known that Set7 catalyzes mono-methylation of histone and non-histone proteins, the functional importance of this enzyme in stem cell differentiation remains poorly understood. We show Set7 expression is increased during mouse embryonic stem cell (mESC) differentiation and is regulated by the pluripotency factors, Oct4 and Sox2. Transcriptional network analyses reveal smooth muscle (SM) associated genes are subject to Set7-mediated regulation. Furthermore, pharmacological inhibition of Set7 activity confirms this regulation. We observe Set7-mediated modification of serum response factor (SRF) and mono-methylation of histone H4 lysine 4 (H3K4me1) regulate gene expression. We conclude the broad substrate specificity of Set7 serves to control key transcriptional networks in embryonic stem cells.
authors.affiliation: Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia.
authors.forename: Natasha K
authors.initials: NK
authors.lastname: Tuano
authors.affiliation: Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia jun.okabe@bakeridi.edu.au.|Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Australia.
authors.forename: Jun
authors.initials: J
authors.lastname: Okabe
authors.affiliation: Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia.|Epigenomic Profiling Facility, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Ziemann
authors.affiliation: Junvenile Diabetes Research Foundation (JDRF) Danielle Alberti Centre for Diabetic Complications, Diabetes Division, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Cooper
authors.affiliation: Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia assam.el-osta@bakeridi.edu.au.|Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Australia.|Epigenomic Profiling Facility, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia.|Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Assam
authors.initials: A
authors.lastname: El-Osta
mesh_terms: D000818:Animals; D000067696:Ataxin-1 / Q000378:metabolism; D015415:Biomarkers; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D016000:Cluster Analysis; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D004789:Enzyme Activation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D010641:Phenotype; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000067696:Ataxin-1; D015415:Biomarkers; D050814:Octamer Transcription Factor-3; D055748:SOXB1 Transcription Factors; D011495:Histone-Lysine N-Methyltransferase