Pleiotrophin antagonizes Brd2 during neuronal differentiation.
Bromodomain-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 Ptn-mediated 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, Ptn-mediated Brd2 antagonism emerges as a modulation system accounting for the balance between cell proliferation and differentiation in the vertebrate nervous system.
['Garcia-Gutierrez|Pablo|P|', 'Juarez-Vicente|Francisco|F|', 'Wolgemuth|Debra J|DJ|', 'Garcia-Dominguez|Mario|M|']
D000818:Animals D002352:Carrier Proteins D002453:Cell Cycle D002454:Cell Differentiation D049109:Cell Proliferation D002843:Chromatin D002868:Chromosomal Proteins, Non-Histone D016207:Cytokines D018507:Gene Expression Regulation, Developmental D057809:HEK293 Cells D006801:Humans D051379:Mice D009432:Neural Crest D055495:Neurogenesis D009474:Neurons D011485:Protein Binding D015202:Protein Engineering D034741:RNA, Small Interfering D013116:Spinal Cord D014157:Transcription Factors
Brd2 Neuronal differentiation Chromatin Ptn