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SIRT1 Inhibits p53 but not NF-?B Transcriptional Activity during Differentiation of Mouse Embryonic Stem Cells into Embryoid Bodies.

ABSTRACT: BACKGROUND AND OBJECTIVES:SIRT1, a histone diacetylase, modify transactivation function of various transcription factor including p53 and NF-?B. p53 and NF-?B is involved in in vitro differentiation of mouse embryonic stem cells (mESC) into mouse embryoid body (mEB). These suggest that SIRT1 might affect in vitro differentiation of mESC into mEB by regulation of p53 and NF-?B. METHODS AND RESULTS:In this study we analyzed the effect of SIRT1 in in vitro differentiation of mESC into mEB using wild and SIRT1 knockout mESC. To examine SIRT1-specific gene in mESC, this study conducted microarray-based differential gene expression analysis between wild and SIRT1 knockout mESC. Comparing their gene expression patterns, this study determined a list of genes regulated by SIRT1. cDNA microarray data-set analysis revealed that genes associated with transcription and signal transduction are significantly modified in SIRT1 knockout mESC. cDNA microarray data-set analysis between mESC and EB in wild and SIRT1 showed that SIRT1 inhibits p53 signaling pathway but not affect NF-?B signaling pathway. CONCLUSIONS:This study suggests that SIRT1 modify mESC differentiation by regulation of p53 transcriptional activity.

SUBMITTER: Lhee SJ

PROVIDER: S-EPMC3840997 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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SIRT1 Inhibits p53 but not NF-κB Transcriptional Activity during Differentiation of Mouse Embryonic Stem Cells into Embryoid Bodies.

Lhee Sang Jae SJ Song Eun-Kyung EK Kim Yu-Ri YR Han Myung-Kwan MK

International journal of stem cells 20121101 2

<h4>Background and objectives</h4>SIRT1, a histone diacetylase, modify transactivation function of various transcription factor including p53 and NF-κB. p53 and NF-κB is involved in in vitro differentiation of mouse embryonic stem cells (mESC) into mouse embryoid body (mEB). These suggest that SIRT1 might affect in vitro differentiation of mESC into mEB by regulation of p53 and NF-κB.<h4>Methods and results</h4>In this study we analyzed the effect of SIRT1 in in vitro differentiation of mESC int ...[more]

PMID: 24298365

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Project description:ObjectiveSexual dimorphism in mammals can be described as subsequent transcriptional differences from their distinct sex chromosome complements. Following X inactivation in females, the Y chromosome is the major genetic difference between sexes. In this study, we used a male embryonic stem cell line (Royan H6) to identify the potential role of the male-specific region of the Y chromosome (MSY) during spontaneous differentiation into embryoid bodies (EBs) as a model of early embryonic development.Materials and methodsIn this experimental study, RH6 cells were cultured on inactivated feeder layers and Matrigel. In a dynamic suspension system, aggregates were generated in the same size and were spontaneously differentiated into EBs. During differentiation, expression patterns of specific markers for three germ layers were compared with MSY genes.ResultsSpontaneous differentiation was determined by downregulation of pluripotent markers and upregulation of fourteen differentiation markers. Upregulation of the ectoderm markers was observed on days 4 and 16, whereas mesoderm markers were upregulated on the 8th day and endodermic markers on days 12-16. Mesoderm markers correlated with 8 MSY genes namely DDX3Y, RPS4Y1, KDM5D, TBL1Y, BCORP1, PRY, DAZ, and AMELY, which were classified as a mesoderm cluster. Endoderm markers were co-expressed with 7 MSY genes, i.e. ZFY, TSPY, PRORY, VCY, EIF1AY, USP9Y, and RPKY, which were grouped as an endoderm cluster. Finally, the ectoderm markers correlated with TXLNGY, NLGN4Y, PCDH11Y, TMSB4Y, UTY, RBMY1, and HSFY genes of the MSY, which were categorized as an ectoderm cluster. In contrast, 2 MSY genes, SRY and TGIF2LY, were more highly expressed in RH6 cells compared to EBs.ConclusionWe found a significant correlation between spontaneous differentiation and upregulation of specific MSY genes. The expression alterations of MSY genes implied the potential responsibility of their gene co-expression clusters for EB differentiation. We suggest that these genes may play important roles in early embryonic development.

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SIRT1 Inhibits p53 but not NF-?B Transcriptional Activity during Differentiation of Mouse Embryonic Stem Cells into Embryoid Bodies.

Publications

SIRT1 Inhibits p53 but not NF-κB Transcriptional Activity during Differentiation of Mouse Embryonic Stem Cells into Embryoid Bodies.

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