title: Unbiased transcriptome signature of in vivo cell proliferation reveals pro- and antiproliferative gene networks.
abstract: Different types of mature B-cell lymphocytes are overall highly similar. Nevertheless, some B cells proliferate intensively, while others rarely do. Here, we demonstrate that a simple binary classification of gene expression in proliferating vs. resting B cells can identify, with remarkable selectivity, global in vivo regulators of the mammalian cell cycle, many of which are also post-translationally regulated by the APC/C E3 ligase. Consequently, we discover a novel regulatory network between the APC/C and the E2F transcription factors and discuss its potential impact on the G1-S transition of the cell cycle. In addition, by focusing on genes whose expression inversely correlates with proliferation, we demonstrate the inherent ability of our approach to also identify in vivo regulators of cell differentiation, cell survival, and other antiproliferative processes. Relying on data sets of wt, non-transgenic animals, our approach can be applied to other cell lineages and human data sets.
authors: The Mina and Everard Goodman Faculty of Life Sciences; Bar-Ilan University; Ramat-Gan, Israel; Advanced Materials and Nanotechnology Institute; Bar-Ilan University; Ramat-Gan, Israel.
authors: Meital
authors: M
authors: Cohen
authors: Manuela
authors: M
authors: Vecsler
authors: Arthur
authors: A
authors: Liberzon
authors: Meirav
authors: M
authors: Noach
authors: Eitan
authors: E
authors: Zlotorynski
authors: Amit
authors: A
authors: Tzur
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D050684:E2F Transcription Factors / Q000378:metabolism; D050687:E2F1 Transcription Factor / Q000378:metabolism; D016193:G1 Phase; D053263:Gene Regulatory Networks; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D016196:S Phase; D059467:Transcriptome; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases
keywords: APC; APC/C; Cdh1; E2F1; E2F7; E2F8; Ubiquitin; atypical E2Fs; cell cycle; differentiation; proliferation; survival; transcriptome
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