title: A comparison of the rest complex binding patterns in embryonic stem cells and epiblast stem cells.
abstract: We detected and characterized the binding sites of the representative Rest complex components Rest, Sin3A, and Lsd1. We compared their binding patterns in mouse embryonic stem (ES) cells and epiblast stem (EpiS) cells. We found few Rest sites unique to the EpiS cells. The ES-unique site features were distinct from those of the common sites, namely, the signal intensities were weaker, and the characteristic gene function categories differed. Our analyses showed that the Rest binding sites do not always overlap with the Sin3A and Lsd1 binding sites. The Sin3A binding pattern differed remarkably between the ES and EpiS cells and was accompanied by significant changes in acetylated-histone patterns in the surrounding regions. A series of transcriptome analyses in the same cell types unexpectedly showed that the putative target gene transcript levels were not dramatically different despite dynamic changes in the Rest complex binding patterns and chromatin statuses, which suggests that Rest is not the sole determinant of repression at its targets. Nevertheless, we identified putative Rest targets with explicitly enhanced transcription upon Rest knock-down in 143 and 60 common and ES-unique Rest target genes, respectively. Among such sites, several genes are involved in ES cell proliferation. In addition, we also found that long, intergenic non-coding RNAs were apparent Rest targets and shared similar features with the protein-coding target genes. Interestingly, such non-coding target genes showed less conservation through evolution than protein-coding targets. As a result of differences in the components and targets of the Rest complex, its functional roles may differ in ES and EpiS cells.
authors.affiliation: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, the University of Tokyo, Kashiwa, Chiba, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Seki
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, the University of Tokyo, Minato-ku, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Masaki
authors.affiliation: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, the University of Tokyo, Kashiwa, Chiba, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Arauchi
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, the University of Tokyo, Minato-ku, Tokyo, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakauchi
authors.affiliation: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, the University of Tokyo, Kashiwa, Chiba, Japan.
authors.forename: Sumio
authors.initials: S
authors.lastname: Sugano
authors.affiliation: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, the University of Tokyo, Kashiwa, Chiba, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001665:Binding Sites; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D005855:Germ Layers / Q000166:cytology / Q000378:metabolism*; D056466:Histone Demethylases; D051379:Mice; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D011485:Protein Binding; D062085:RNA, Long Noncoding / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014158:Transcription, Genetic; D000099229:RE1-Silencing Transcription Factor
chemical_list: D002843:Chromatin; D056466:Histone Demethylases; D010089:Oxidoreductases, N-Demethylating; D062085:RNA, Long Noncoding; D012097:Repressor Proteins; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D000099229:RE1-Silencing Transcription Factor; C099683:SIN3A transcription factor; C504076:KDM1a protein, mouse
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