title: Lineage-specific interface proteins match up the cell cycle and differentiation in embryo stem cells.
abstract: The shortage of molecular information on cell cycle changes along embryonic stem cell (ESC) differentiation prompts an in silico approach, which may provide a novel way to identify candidate genes or mechanisms acting in coordinating the two programs. We analyzed germ layer specific gene expression changes during the cell cycle and ESC differentiation by combining four human cell cycle transcriptome profiles with thirteen in vitro human ESC differentiation studies. To detect cross-talk mechanisms we then integrated the transcriptome data that displayed differential regulation with protein interaction data. A new class of non-transcriptionally regulated genes was identified, encoding proteins which interact systematically with proteins corresponding to genes regulated during the cell cycle or cell differentiation, and which therefore can be seen as interface proteins coordinating the two programs. Functional analysis gathered insights in fate-specific candidates of interface functionalities. The non-transcriptionally regulated interface proteins were found to be highly regulated by post-translational ubiquitylation modification, which may synchronize the transition between cell proliferation and differentiation in ESCs.
authors.affiliation: Laboratory of Translational Genomics, Centre for Integrative Biology, University of Trento, Via delle Regole 101, I38123 Trento, Italy; Center for Biological Sequence Analysis, Technical University of Denmark, Kemitorvet, DK2800 Lyngby, Denmark.
authors.forename: Angela
authors.initials: A
authors.lastname: Re
authors.affiliation: Center for Biological Sequence Analysis, Technical University of Denmark, Kemitorvet, DK2800 Lyngby, Denmark.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Workman
authors.affiliation: City University of New York School of Public Health, Hunter College, 2180 3rd Avenue, NY 10035, USA.
authors.forename: Levi
authors.initials: L
authors.lastname: Waldron
authors.affiliation: Laboratory of Translational Genomics, Centre for Integrative Biology, University of Trento, Via delle Regole 101, I38123 Trento, Italy. Electronic address: alessandro.quattrone@unitn.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Quattrone
authors.affiliation: Center for Biological Sequence Analysis, Technical University of Denmark, Kemitorvet, DK2800 Lyngby, Denmark; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Blegdamsvej 3B, DK2200 Copenhagen, Denmark. Electronic address: brunak@cbs.dtu.dk.
authors.forename: Søren
authors.initials: S
authors.lastname: Brunak
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D030541:Databases, Genetic; D053595:Embryonic Stem Cells / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D005838:Genotype; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D060066:Protein Interaction Maps; D015398:Signal Transduction; D013997:Time Factors; D054875:Ubiquitination
chemical_list: D018797:Cell Cycle Proteins