title: Promyelocytic leukemia protein in retinoic acid-induced chromatin remodeling of Oct4 gene promoter.
abstract: Promyelocytic leukemia (Pml) protein is required for Oct4 gene expression and the maintenance of its open chromatin conformation in stem cells. In proliferating stem cells, Pml-nuclear body, along with transcription factors TR2, steroidogenic factor 1 (SF1) and Sp1, and Brg1-dependent chromatin remodeling complex (BRGC), associates with conserved region 1 (CR1) of this promoter to maintain a nucleosome-free region for gene activity. Retinoic acid (RA) rapidly downregulates Pml, resulting in the replacement of BRGC with Brm-containing remodeling complex, disassociation of SF1 and Sp1, retaining of TR2, recruitment of receptor-interaction protein 140, G9a and HP1γ, and sequential insertion of two nucleosomes on CR1 that progressively displays repressive heterochromatin marks. This study demonstrates a functional role for Pml in maintaining a specific open chromatin conformation of the Oct4 promoter region for its constant expression in stem cells; and illustrates the mechanism underlying RA-induced chromatin remodeling of Oct4 gene in differentiating cells, in which Pml plays a critical role. The study also demonstrates a novel mode of chromatin remodeling, which occurs by repositioning and sequentially inserting nucleosomes into a specific region of the gene promoter to compact the chromatin in differentiating cells.
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors.forename: Ya-Shan
authors.initials: YS
authors.lastname: Chuang
authors.forename: Wei-Hong
authors.initials: WH
authors.lastname: Huang
authors.forename: Sung Wook
authors.initials: SW
authors.lastname: Park
authors.forename: Shawna D
authors.initials: SD
authors.lastname: Persaud
authors.forename: Chen-Hsiang
authors.initials: CH
authors.lastname: Hung
authors.forename: Ping-Chih
authors.initials: PC
authors.lastname: Ho
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Wei
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000378:metabolism*; D009707:Nucleosomes; D050814:Octamer Transcription Factor-3 / Q000235:genetics*; D011401:Promoter Regions, Genetic; D000071156:Promyelocytic Leukemia Protein; D034622:RNA Interference; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016329:Sp1 Transcription Factor / Q000378:metabolism; D054339:Steroidogenic Factor 1 / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D009707:Nucleosomes; D050814:Octamer Transcription Factor-3; C513293:Pml protein, mouse; C494174:Pou5f1 protein, mouse; D000071156:Promyelocytic Leukemia Protein; D034741:RNA, Small Interfering; D016329:Sp1 Transcription Factor; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014212:Tretinoin