title: Control of neuronal differentiation by sumoylation of BRAF35, a subunit of the LSD1-CoREST histone demethylase complex.
abstract: The LSD1-CoREST histone demethylase complex is required to repress neuronal genes in nonneuronal tissues. Here we show that sumoylation of Braf35, one of the subunits of the complex, is required to maintain full repression of neuron-specific genes and for occupancy of the LSD1-CoREST complex at its gene targets. Interestingly, expression of Braf35 was sufficient to prevent neuronal differentiation induced by bHLH neurogenic transcription factors in P19 cells and in neuronal progenitors of the chicken embryo neural tube. Sumoylation of Braf35 is required for this antineurogenic activity. We also show that iBraf, a paralogue of Braf35, forms heterodimers with Braf35. Braf35-iBraf heterodimerization impairs Braf35 interaction with the LSD1-CoREST complex and inhibits Braf35 sumoylation. Consistent with these results, iBraf prevents the antineurogenic activity of Braf35 in vivo. Our data uncover a mechanism of regulation of the LSD1-CoREST complex and provide a molecular explanation for the antagonism between Braf35 and iBraf in neuronal differentiation.
authors.affiliation: Department of Molecular Biology, Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Consejo Superior de Investigaciones Científicas-Universidad de Sevilla-Junta de Andalucía, 41092 Seville, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Ceballos-Chávez
authors.forename: Sabrina
authors.initials: S
authors.lastname: Rivero
authors.forename: Pablo
authors.initials: P
authors.lastname: García-Gutiérrez
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodríguez-Paredes
authors.forename: Mario
authors.initials: M
authors.lastname: García-Domínguez
authors.forename: Shomi
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: José C
authors.initials: JC
authors.lastname: Reyes
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000502:physiology; D002642:Chick Embryo; D002645:Chickens; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D019281:Dimerization; D054278:Embryonal Carcinoma Stem Cells / Q000166:cytology; D005786:Gene Expression Regulation / Q000502:physiology; D057809:HEK293 Cells; D006367:HeLa Cells; D006609:High Mobility Group Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056466:Histone Demethylases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D051379:Mice; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology*; D010089:Oxidoreductases, N-Demethylating / Q000737:chemistry / Q000378:metabolism*; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D058207:Sumoylation / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; C507322:Hmg20a protein, mouse; C400291:Hmg20b protein, mouse; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; C485650:Rcor2 protein, mouse; D012097:Repressor Proteins; D056466:Histone Demethylases; C504076:KDM1a protein, mouse; D010089:Oxidoreductases, N-Demethylating