title: Small-Activating RNA Can Change Nucleosome Positioning in Human Fibroblasts.
abstract: RNA activation (RNAa) is a mechanism of positive gene expression regulation mediated by small-activating RNAs (saRNAs), which target gene promoters and have been used as tools to manipulate gene expression. Studies have shown that RNAa is associated with epigenetic modifications at promoter regions; however, it is unclear whether these modifications are the cause or a consequence of RNAa. In this study, we examined changes in nucleosome repositioning and the involvement of RNA polymerase II (RNAPII) in this process. We screened saRNAs for OCT4 (POU5F1), SOX2, and NANOG, and identified several novel saRNAs. We found that nucleosome positioning was altered after saRNA treatment and that the formation of nucleosome-depleted regions (NDRs) contributed to RNAa at sites of RNAPII binding, such as the TATA box, CpG islands (CGIs), proximal enhancers, and proximal promoters. Moreover, RNAPII appeared to be bound specifically to NDRs. These results suggested that changes in nucleosome positions resulted from RNAa. We thus propose a hypothesis that targeting promoter regions using exogenous saRNAs can induce the formation of NDRs, exposing regulatory binding sites to recruit RNAPII, a key component of preinitiation complex, and leading to increased initiation of transcription.
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China Department of Biology, Kunming University, Kunming, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Biology, Kunming University, Kunming, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Biology, Kunming University, Kunming, China.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Tong
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
authors.forename: Ningzhu
authors.initials: N
authors.lastname: Hu
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China huyunzhangym@126.com.
authors.forename: YunZhang
authors.initials: Y
authors.lastname: Hu
mesh_terms: D001665:Binding Sites; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D000071317:Nanog Homeobox Protein / Q000235:genetics; D009707:Nucleosomes / Q000235:genetics* / Q000648:ultrastructure; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D011401:Promoter Regions, Genetic; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D012319:RNA Polymerase II / Q000235:genetics* / Q000378:metabolism; D058727:RNA, Small Untranslated / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D009707:Nucleosomes; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D058727:RNA, Small Untranslated; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D012313:RNA; D012319:RNA Polymerase II
keywords: RNAPII; RNAa; nucleosome repositioning; nucleosome-depleted region; small-activating RNA