title: A synthetic small molecule for rapid induction of multiple pluripotency genes in mouse embryonic fibroblasts.
abstract: Cellular reprogramming involves profound alterations in genome-wide gene expression that is precisely controlled by a hypothetical epigenetic code. Small molecules have been shown to artificially induce epigenetic modifications in a sequence independent manner. Recently, we showed that specific DNA binding hairpin pyrrole-imidazole polyamides (PIPs) could be conjugated with chromatin modifying histone deacetylase inhibitors like SAHA to epigenetically activate certain pluripotent genes in mouse fibroblasts. In our steadfast progress to improve the efficiency of SAHA-PIPs, we identified a novel compound termed, δ that could dramatically induce the endogenous expression of Oct-3/4 and Nanog. Genome-wide gene analysis suggests that in just 24 h and at nM concentration, δ induced multiple pluripotency-associated genes including Rex1 and Cdh1 by more than ten-fold. δ treated MEFs also rapidly overcame the rate-limiting step of epithelial transition in cellular reprogramming by switching "[Formula: see text]" the complex transcriptional gene network.
authors: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Sakyo, Kyoto 606-8502, Japan.
authors: Ganesh N
authors: GN
authors: Pandian
authors: Yusuke
authors: Y
authors: Nakano
authors: Shinsuke
authors: S
authors: Sato
authors: Hironobu
authors: H
authors: Morinaga
authors: Toshikazu
authors: T
authors: Bando
authors: Hiroki
authors: H
authors: Nagase
authors: Hiroshi
authors: H
authors: Sugiyama
mesh_terms: D000107:Acetylation; D000818:Animals; D065150:Cellular Reprogramming / Q000187:drug effects*; D044127:Epigenesis, Genetic / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism; D051379:Mice; D011401:Promoter Regions, Genetic
chemical_list: D056572:Histone Deacetylase Inhibitors