Genomic and proteomic analyses of Prdm5 reveal interactions with insulator binding proteins in embryonic stem cells

Giorgio Giacomo Galli, Matteo Carrara, Chiara Francavilla, Kristian Honnens de Lichtenberg, Jesper Velgaard Olsen, Raffaele Adolfo Calogero, Anders H. Lund

24 Citations (Scopus)

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 nextgeneration 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.

Original languageEnglish
JournalMolecular and Cellular Biology
ISSN0270-7306
DOIs
Publication statusPublished - 15 Nov 2013

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