title: Genomic and proteomic analyses of Prdm5 reveal interactions with insulator binding proteins in embryonic stem cells.
abstract: PRDM proteins belong to the SET domain protein family, which is involved in the regulation of gene expression. Although few PRDM members possess histone methyltransferase activity, the molecular mechanisms by which the other members exert transcriptional regulation remain to be delineated. In this study, we find that Prdm5 is highly expressed in mouse embryonic stem (mES) cells and exploit this cellular system to characterize molecular functions of Prdm5. By combining proteomics and next-generation sequencing technologies, we identify Prdm5 interaction partners and genomic occupancy. We demonstrate that although Prdm5 is dispensable for mES cell maintenance, it directly targets genomic regions involved in early embryonic development and affects the expression of a subset of developmental regulators during cell differentiation. Importantly, Prdm5 interacts with Ctcf, cohesin, and TFIIIC and cooccupies genomic loci. In summary, our data indicate how Prdm5 modulates transcription by interacting with factors involved in genome organization in mouse embryonic stem cells.
authors.affiliation: Biotech Research and Innovation Centre and Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Giorgio Giacomo
authors.initials: GG
authors.lastname: Galli
authors.forename: Matteo
authors.initials: M
authors.lastname: Carrara
authors.forename: Chiara
authors.initials: C
authors.lastname: Francavilla
authors.forename: Kristian Honnens
authors.initials: KH
authors.lastname: de Lichtenberg
authors.forename: Jesper Velgaard
authors.initials: JV
authors.lastname: Olsen
authors.forename: Raffaele Adolfo
authors.initials: RA
authors.lastname: Calogero
authors.forename: Anders Henrik
authors.initials: AH
authors.lastname: Lund
mesh_terms: D000818:Animals; D000076246:CCCTC-Binding Factor; D002454:Cell Differentiation; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D051379:Mice; D009154:Mutation; D011485:Protein Binding; D060066:Protein Interaction Maps; D040901:Proteomics; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D019474:Transcription Factors, TFIII / Q000378:metabolism; D000098832:Transcription Factor TFIIIC
chemical_list: D000076246:CCCTC-Binding Factor; D002843:Chromatin; C000619698:Ctcf protein, mouse; D004268:DNA-Binding Proteins; C575119:PRDM5 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D019474:Transcription Factors, TFIII; D000098832:Transcription Factor TFIIIC
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