title: Suppression of Sin3A activity promotes differentiation of pluripotent cells into functional neurons.
abstract: Sin3 is a transcriptional corepressor for REST silencing machinery that represses multiple neuronal genes in non-neuronal cells. However, functions of Sin3 (Sin3A and Sin3B) in suppression of neuronal phenotypes are not well characterized. Herein we show that Sin3A knockdown impedes the repressive activity of REST and enhances differentiation of pluripotent P19 cells into electrophysiologically active neurons without inducing astrogenesis. It is also found that silencing Sin3B induces neurogenesis of P19 cells with a lower efficiency than Sin3A knockdown. The results suggest that Sin3A has a more profound effect on REST repressive machinery for silencing neuronal genes in P19 cells than Sin3B. Furthermore, we show that a peptide inhibitor of Sin3A-REST interactions promotes differentiation of P19 cells into functional neurons. Observations made in studies using genetic deletion and a synthetic inhibitor suggests that Sin3A plays an important role in the repression of neuronal genes by the REST regulatory mechanism.
authors.affiliation: National Creative Research Initiative Center for Biofunctional Molecules, Department of Chemistry, Yonsei University, Seoul 03722, Korea.
authors.forename: Debasish
authors.initials: D
authors.lastname: Halder
authors.affiliation: National Creative Research Initiative Center for Biofunctional Molecules, Department of Chemistry, Yonsei University, Seoul 03722, Korea.
authors.forename: Chang-Hee
authors.initials: CH
authors.lastname: Lee
authors.affiliation: National Creative Research Initiative Center for Biofunctional Molecules, Department of Chemistry, Yonsei University, Seoul 03722, Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Hyun
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
authors.forename: Gyeong-Eon
authors.initials: GE
authors.lastname: Chang
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
authors.forename: Eunji
authors.initials: E
authors.lastname: Cheong
authors.affiliation: National Creative Research Initiative Center for Biofunctional Molecules, Department of Chemistry, Yonsei University, Seoul 03722, Korea.
authors.forename: Injae
authors.initials: I
authors.lastname: Shin
mesh_terms: D000200:Action Potentials / Q000235:genetics; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D015415:Biomarkers; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D057846:Cell-Penetrating Peptides / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D010641:Phenotype; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D056264:Sin3 Histone Deacetylase and Corepressor Complex
chemical_list: D015415:Biomarkers; D057846:Cell-Penetrating Peptides; D012097:Repressor Proteins; C099683:SIN3A transcription factor; D056264:Sin3 Histone Deacetylase and Corepressor Complex