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Title

Pleiotrophin antagonizes Brd2 during neuronal differentiation

AuthorsGarcía-Gutiérrez, Pablo ; Juárez-Vicente, Francisco ; Wolgemuth, Debra J.; García-Domínguez, Mario
KeywordsBrd2
Ptn
Neuronal differentiation
Chromatin
Issue Date2014
PublisherCompany of Biologists
CitationJournal of Cell Science 127: 2554-2564 (2014)
AbstractBromodomain-containing protein 2 (Brd2) is a BET family chromatin adaptor required for expression of cell-cycle-associated genes and therefore involved in cell cycle progression. Brd2 is expressed in proliferating neuronal progenitors, displays cell-cycle-stimulating activity and, when overexpressed, impairs neuronal differentiation. Paradoxically, Brd2 is also detected in differentiating neurons. To shed light on the role of Brd2 in the transition from cell proliferation to differentiation, we had previously looked for proteins that interacted with Brd2 upon induction of neuronal differentiation. Surprisingly, we identified the growth factor pleiotrophin (Ptn). Here, we show that Ptn antagonized the cell-cycle-stimulating activity associated with Brd2, thus enhancing induced neuronal differentiation. Moreover, Ptn knockdown reduced neuronal differentiation. We analyzed Ptnmediated antagonism of Brd2 in a cell differentiation model and in two embryonic processes associated with the neural tube: spinal cord neurogenesis and neural crest migration. Finally, we investigated the mechanisms of Ptn-mediated antagonism and determined that Ptn destabilizes the association of Brd2 with chromatin. Thus, Ptnmediated Brd2 antagonism emerges as a modulation system accounting for the balance between cell proliferation and differentiation in the vertebrate nervous system. © 2014. Published by The Company of Biologists Ltd.
Publisher version (URL)http://dx.doi.org/10.1242/jcs.147462
URIhttp://hdl.handle.net/10261/123507
DOI10.1242/jcs.147462
Identifiersdoi: 10.1242/jcs.147462
issn: 1477-9137
Appears in Collections:(CABIMER) Artículos
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