title: Systematic identification of gene family regulators in mouse and human embryonic stem cells.
abstract: Pluripotent self-renewing embryonic stem cells (ESCs) have been the focus of a growing number of high-throughput experiments, revealing the genome-wide locations of hundreds of transcription factors and histone modifications. While most of these datasets were used in a specific context, all datasets combined offer a comprehensive view of chromatin characteristics and regulatory elements that govern cell states. Here, using hundreds of datasets in ESCs, we generated colocalization maps of chromatin proteins and modifications, and built a discovery pipeline for regulatory proteins of gene families. By comparing genome-wide binding data with over-expression and knockdown analysis of hundreds of genes, we discovered that the pluripotency-related factor NR5A2 separates mitochondrial from cytosolic ribosomal genes, regulating their expression. We further show that genes with a common chromatin profile are enriched for distinct Gene Ontology (GO) categories. Our approach can be generalized to reveal common regulators of any gene group; discover novel gene families, and identify common genomic elements based on shared chromatin features.
authors.affiliation: Department of Genetics, The Alexander Silberman Institute of Life Sciences, Jerusalem 91904, Israel.
authors.forename: Yair
authors.initials: Y
authors.lastname: Aaronson
authors.affiliation: Department of Genetics, The Alexander Silberman Institute of Life Sciences, Jerusalem 91904, Israel.
authors.forename: Ilana
authors.initials: I
authors.lastname: Livyatan
authors.affiliation: Department of Genetics, The Alexander Silberman Institute of Life Sciences, Jerusalem 91904, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Gokhman
authors.affiliation: Department of Genetics, The Alexander Silberman Institute of Life Sciences, Jerusalem 91904, Israel The Edmond and Lily Center for Brain Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Jerusalem 91904, Israel meshorer@huji.ac.il.
authors.forename: Eran
authors.initials: E
authors.lastname: Meshorer
mesh_terms: D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation / Q000235:genetics; D002843:Chromatin / Q000235:genetics*; D006657:Histones / Q000235:genetics; D000066449:Human Embryonic Stem Cells / Q000166:cytology*; D006801:Humans; D051379:Mice; D000069396:Mitochondrial Ribosomes / Q000378:metabolism; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D002843:Chromatin; D006657:Histones; C082631:NR5A2 protein, human; C431936:Nr5a2 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D012269:Ribosomal Proteins; D014157:Transcription Factors