Suppression of Sin3A activity promotes differentiation of pluripotent cells into functional neurons

Debasish Halder, Chang Hee Lee, Ji Young Hyun, Gyeong Eon Chang, Eunji Cheong, Injae Shin

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Article number44818
JournalScientific reports
Volume7
DOIs
Publication statusPublished - 2017 Mar 17

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Cell Differentiation
Neurons
Co-Repressor Proteins
Neurogenesis
Gene Silencing
Regulator Genes
Phenotype
Peptides
Genes

All Science Journal Classification (ASJC) codes

  • General

Cite this

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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.",
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Suppression of Sin3A activity promotes differentiation of pluripotent cells into functional neurons. / Halder, Debasish; Lee, Chang Hee; Hyun, Ji Young; Chang, Gyeong Eon; Cheong, Eunji; Shin, Injae.

In: Scientific reports, Vol. 7, 44818, 17.03.2017.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Halder, Debasish

AU - Lee, Chang Hee

AU - Hyun, Ji Young

AU - Chang, Gyeong Eon

AU - Cheong, Eunji

AU - Shin, Injae

PY - 2017/3/17

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AB - 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.

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