TY - JOUR
T1 - The BAF complex interacts with Pax6 in adult neural progenitors to establish a neurogenic cross-regulatory transcriptional network
AU - Ninkovic, Jovica
AU - Steiner-Mezzadri, Andrea
AU - Jawerka, Melanie
AU - Akinci, Umut
AU - Masserdotti, Giacomo
AU - Petricca, Stefania
AU - Fischer, Judith
AU - Von Holst, Alexander
AU - Beckers, Johanes
AU - Lie, Chichung D.
AU - Petrik, David
AU - Miller, Erik
AU - Tang, Jiong
AU - Wu, Jiang
AU - Lefebvre, Veronique
AU - Demmers, Jeroen
AU - Eisch, Amelia
AU - Metzger, Daniel
AU - Crabtree, Gerald
AU - Irmler, Martin
AU - Poot, Raymond
AU - Götz, Magdalena
N1 - Funding Information:
We want to thank Peter Becker, Ales Cvekl, and Maren Eckey for help with establishment of ChIP experiments, and Karel Bezstarosti for help with the mass spectrometry analysis. We are also thankful to Timucin Özturk, Emily Violette-Baumgardt, and Angelika Waiser for excellent technical help, Alexandra Lepier for the viral vector production, Jelena Ninkovic for the help with statistical analysis, and Leda Dimou for critical reading of the manuscript. We also gratefully acknowledge funding to J.N. from the German Research foundation (DFG) by the SFB 870 and SPP “Integrative Analysis of Olfaction,” and to M.G. from the German Research foundation (DFG) by the SFB 870, the Leibniz Prize, and the Munich Cluster for Systems Neurology (EXC 1010 SyNergy).
PY - 2013/10/3
Y1 - 2013/10/3
N2 - Numerous transcriptional regulators of neurogenesis have been identified in the developing and adult brain, but how neurogenic fate is programmed at the epigenetic level remains poorly defined. Here, we report that the transcription factor Pax6 directly interacts with the Brg1-containing BAF complex in adult neural progenitors. Deletion of either Brg1 or Pax6 in the subependymal zone (SEZ) causes the progeny of adult neural stem cells to convert to the ependymal lineage within the SEZ while migrating neuroblasts convert to different glial lineages en route to or in the olfactory bulb (OB). Genome-wide analyses reveal that the majority of genes downregulated in the Brg1 null SEZ and OB contain Pax6 binding sites and are also downregulated in Pax6 null SEZ and OB. Downstream of the Pax6-BAF complex, we find that Sox11, Nfib, and Pou3f4 form a transcriptional cross-regulatory network that drives neurogenesis and can convert postnatal glia into neurons. Taken together, elements of our work identify a tripartite effector network activated by Pax6-BAF that programs neuronal fate.
AB - Numerous transcriptional regulators of neurogenesis have been identified in the developing and adult brain, but how neurogenic fate is programmed at the epigenetic level remains poorly defined. Here, we report that the transcription factor Pax6 directly interacts with the Brg1-containing BAF complex in adult neural progenitors. Deletion of either Brg1 or Pax6 in the subependymal zone (SEZ) causes the progeny of adult neural stem cells to convert to the ependymal lineage within the SEZ while migrating neuroblasts convert to different glial lineages en route to or in the olfactory bulb (OB). Genome-wide analyses reveal that the majority of genes downregulated in the Brg1 null SEZ and OB contain Pax6 binding sites and are also downregulated in Pax6 null SEZ and OB. Downstream of the Pax6-BAF complex, we find that Sox11, Nfib, and Pou3f4 form a transcriptional cross-regulatory network that drives neurogenesis and can convert postnatal glia into neurons. Taken together, elements of our work identify a tripartite effector network activated by Pax6-BAF that programs neuronal fate.
UR - http://www.scopus.com/inward/record.url?scp=84885128467&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2013.07.002
DO - 10.1016/j.stem.2013.07.002
M3 - Article
C2 - 23933087
AN - SCOPUS:84885128467
SN - 1934-5909
VL - 13
SP - 403
EP - 418
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 4
ER -