E2F1 coregulates cell cycle genes and chromatin components during the transition of oligodendrocyte progenitors from proliferation to differentiation

Laura Magri, Victoria A. Swiss, Beata Jablonska, Liang Lei, Xiomara Pedre, Martin Walsh, Weijia Zhang, Vittorio Gallo, Peter Canoll, Patrizia Casaccia

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Cell cycle exit is an obligatory step for the differentiation of oligodendrocyte progenitor cells (OPCs) into myelinating cells. A key regulator of the transition from proliferation to quiescence is the E2F/Rb pathway, whose activity is highly regulated in physiological conditions and deregulated in tumors. In this paper we report a lineage-specific decline of nuclear E2F1 during differentiation of rodent OPC into oligodendrocytes (OLs) in developing white matter tracts and in cultured cells. Using chromatin immunoprecipitation (ChIP) and deep-sequencing in mouse and rat OPCs, we identified cell cycle genes (i.e., Cdc2) and chromatin components (i.e., Hmgn1, Hmgn2), including those modulating DNA methylation (i.e., Uhrf1), as E2F1 targets. Binding of E2F1 to chromatin on the gene targets was validated and their expression assessed in developing white matter tracts and cultured OPCs. Increased expression of E2F1 gene targets was also detected in mouse gliomas (that were induced by retroviral transformation of OPCs) compared with normal brain. Together, these data identify E2F1 as a key transcription factor modulating the expression of chromatin components in OPC during the transition from proliferation to differentiation.

Original languageEnglish
Pages (from-to)1481-1493
Number of pages13
JournalJournal of Neuroscience
Volume34
Issue number4
DOIs
StatePublished - 2014

Keywords

  • Brain
  • Cell cycle
  • Chromatin
  • Development
  • Tumor

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