Unbiased transcriptome signature of in vivo cell proliferation reveals pro- and antiproliferative gene networks

Meital Cohen, Manuela Vecsler, Arthur Liberzon, Meirav Noach, Eitan Zlotorynski, Amit Tzur

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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.

Original languageEnglish
Pages (from-to)2992-3000
Number of pages9
JournalCell Cycle
Volume12
Issue number18
DOIs
StatePublished - 15 Sep 2013

Bibliographical note

Funding Information:
We are deeply indebted to Dr Jane Seagal for introducing us to the wonders of immunology, and to Prof Doron Ginsberg for reagents. Funding by the Israeli Centers of Research Excellence (I-CORE), Gene Regulation in Complex Human Disease, Center No. 41/11 (AT); the Israel Cancer Association Grant 20120067 (AT); the German–Israeli Foundation (GIF), No. 2294-2269.2/2011 (AT); and the Israel Cancer Research Fund (ICRF) postdoctoral fellowship (MV) is gratefully acknowledged.

Keywords

  • APC
  • APC/C
  • Atypical E2Fs
  • Cdh1
  • Cell cycle
  • Differentiation
  • E2F1
  • E2F7
  • E2F8
  • Proliferation
  • Sur vival
  • Transcriptome
  • Ubiquitin

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