RT Journal Article
SR Electronic
T1 E2F1 Coregulates Cell Cycle Genes and Chromatin Components during the Transition of Oligodendrocyte Progenitors from Proliferation to Differentiation
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1481
OP 1493
DO 10.1523/JNEUROSCI.2840-13.2014
VO 34
IS 4
A1 Laura Magri
A1 Victoria A. Swiss
A1 Beata Jablonska
A1 Liang Lei
A1 Xiomara Pedre
A1 Martin Walsh
A1 Weijia Zhang
A1 Vittorio Gallo
A1 Peter Canoll
A1 Patrizia Casaccia
YR 2014
UL http://www.jneurosci.org/content/34/4/1481.abstract
AB 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.