title: Sodium butyrate facilitates reprogramming by derepressing OCT4 transactivity at the promoter of embryonic stem cell-specific miR-302/367 cluster.
abstract: Small-molecule inhibitors and microRNAs (miRNAs) are two newly emerging classes of tools for optimizing induced pluripotent stem cell (iPSC) generation. We report here that sodium butyrate (NaB), a small-molecule inhibitor of histone deacetylases (HDACs), upregulates transcriptional levels of the miR-302/367 cluster by enhancing Oct4 transcriptional activity at the miR-302/367 cluster promoter. NaB does not affect the OCT4 DNA-binding domain; instead it enhances transactivity of the OCT4 transactivation domains. We elucidate that OCT4 transcriptional activity is usually dampened by its associated HDACs in cells and can be derepressed by NaB by impairing the interaction between Oct4 and HDACs, which leads to an elevated expression of the miR-302/367 cluster. Our new findings suggest a novel molecular mechanism for NaB in promoting somatic cell reprogramming via the miR-302/367 cluster.
authors.affiliation: 1 Section of Hematology/Oncology, Department of Medicine, and UIC Cancer Center, University of Illinois at Chicago. Chicago , IL, 60612.
authors.forename: Zhonghui
authors.initials: Z
authors.lastname: Zhang
authors.forename: Di
authors.initials: D
authors.lastname: Xiang
authors.forename: Wen-Shu
authors.initials: WS
authors.lastname: Wu
mesh_terms: D020148:Butyric Acid / Q000494:pharmacology*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006633:Histamine Antagonists / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D005810:Multigene Family; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation / Q000187:drug effects*
chemical_list: D006633:Histamine Antagonists; D056572:Histone Deacetylase Inhibitors; C568081:MIRN367 microRNA, human; D035683:MicroRNAs; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D020148:Butyric Acid