title: Differentiation and upregulation of heat shock protein 70 induced by a subset of histone deacetylase inhibitors in mouse and human embryonic stem cells.
abstract: Inhibiting histone deacetylase (HDAC) activity modulates the epigenetic status of cells, resulting in an alteration of gene expression and cellular function. Here, we investigated the effects of HDAC inhibitors on mouse embryonic stem (ES) cells. The HDAC inhibitors trichostatin A, suberoylanilide hydroxamic acid, sodium butyrate, and valproic acid induced early differentiation of mouse ES cells and triggered induction of heatshock protein (HSP)70. In contrast, class III HDAC inhibitors failed to induce differentiation or HSP70 expression. Transcriptional upregulation of HSP70 was confirmed by mRNA expression analysis, an inhibitor study, and chromatin immunoprecipitation. HSP70 induction was dependent on the SAPK/ JNK, p38, and PI3K/Akt pathways. Differentiation and induction of HSP70 by a subset of HDAC inhibitors was also examined in human ES cells, which suggests that the phenomenon generally occurs in ES cells. A better understanding of the effects of HDAC inhibitors may give more insight into their application in stem cell biology.
authors.affiliation: Biotechnology Research Institute, Chungbuk National University, Cheongju, Korea.
authors.forename: Jeong-A
authors.initials: JA
authors.lastname: Park
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Kim
authors.forename: Hyun-Jeong
authors.initials: HJ
authors.lastname: Seok
authors.forename: Woo-Youn
authors.initials: WY
authors.lastname: Park
authors.forename: Hyung-Joo
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Younghee
authors.initials: Y
authors.lastname: Lee
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D057890:Epigenomics; D005786:Gene Expression Regulation / Q000187:drug effects*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D018840:HSP70 Heat-Shock Proteins; D056572:Histone Deacetylase Inhibitors; D011494:Protein Kinases