title: Reverse engineering a mouse embryonic stem cell-specific transcriptional network reveals a new modulator of neuronal differentiation.
abstract: Gene expression profiles can be used to infer previously unknown transcriptional regulatory interaction among thousands of genes, via systems biology 'reverse engineering' approaches. We 'reverse engineered' an embryonic stem (ES)-specific transcriptional network from 171 gene expression profiles, measured in ES cells, to identify master regulators of gene expression ('hubs'). We discovered that E130012A19Rik (E13), highly expressed in mouse ES cells as compared with differentiated cells, was a central 'hub' of the network. We demonstrated that E13 is a protein-coding gene implicated in regulating the commitment towards the different neuronal subtypes and glia cells. The overexpression and knock-down of E13 in ES cell lines, undergoing differentiation into neurons and glia cells, caused a strong up-regulation of the glutamatergic neurons marker Vglut2 and a strong down-regulation of the GABAergic neurons marker GAD65 and of the radial glia marker Blbp. We confirmed E13 expression in the cerebral cortex of adult mice and during development. By immuno-based affinity purification, we characterized protein partners of E13, involved in the Polycomb complex. Our results suggest a role of E13 in regulating the division between glutamatergic projection neurons and GABAergic interneurons and glia cells possibly by epigenetic-mediated transcriptional regulation.
authors.affiliation: Telethon Institute of Genetics and Medicine, Via P. Castellino 111, Napoli 80131, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: De Cegli
authors.forename: Simona
authors.initials: S
authors.lastname: Iacobacci
authors.forename: Gemma
authors.initials: G
authors.lastname: Flore
authors.forename: Gennaro
authors.initials: G
authors.lastname: Gambardella
authors.forename: Lei
authors.initials: L
authors.lastname: Mao
authors.forename: Luisa
authors.initials: L
authors.lastname: Cutillo
authors.forename: Mario
authors.initials: M
authors.lastname: Lauria
authors.forename: Joachim
authors.initials: J
authors.lastname: Klose
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Illingworth
authors.forename: Sandro
authors.initials: S
authors.lastname: Banfi
authors.forename: Diego
authors.initials: D
authors.lastname: di Bernardo
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone; D053595:Embryonic Stem Cells / Q000378:metabolism*; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics*; D025941:Protein Interaction Mapping; D049490:Systems Biology / Q000379:methods; D059467:Transcriptome; D019076:Transgenes
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C579430:Epop protein, mouse; D009419:Nerve Tissue Proteins