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Promoter-Targeted Small Activating RNAs Alter Nucleosome Positioning

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RNA Activation

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 983))

Abstract

Epigenetic modification of target promoters has been identified as a mechanism underlying RNA activation (RNAa) induced by promoter-targeting small activating RNAs (saRNAs), but it is unclear how the chromosomal environment influences gene expression. In a study of the activation of the OCT4, SOX2, and NANOG genes by saRNAs, we found that saRNA targeting induced nucleosome-depleted region (NDRs) and the accumulation of RNA polymerase II (RNAPII) near or at the saRNA target sites. Additionally, promoters containing certain cis-regulatory elements such as the TATA box and CpG islands (CGIs) appeared to be more susceptible to RNAa. These results provide novel insight into the mechanism underlying RNAa in that saRNAs induce NDRs in the target promoter to remove nucleosome barriers between RNAPII-binding sites and the transcription start site (TSS), resulting in rapid assembly of transcription preinitiation complex (PIC) and subsequent activation of transcription.

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References

  1. Britten RJ, Davidson EH (1969) Gene regulation for higher cells: a theory. Science 165(3891):349–357

    Article  CAS  PubMed  Google Scholar 

  2. Dikstein R (2012) The unexpected traits associated with core promoter elements. Transcription 2(5):201–206

    Article  Google Scholar 

  3. Floer M, Wang X, Prabhu V, Berrozpe G, Narayan S, Dan S, Alvarez D, Kendall J, Krasnitz A, Stepansky A (2010) A RSC/nucleosome complex determines chromatin architecture and facilitates activator binding. Cell 141(3):407–418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Gui CY, Dean A (2003) A major role for the TATA box in recruitment of chromatin modifying complexes to a globin gene promoter. Proc Natl Acad Sci U S A 100(12):7009–7014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Higgs DR (1998) Do lcrs open chromatin domains? Cell 95(3):299–302

    Article  CAS  PubMed  Google Scholar 

  6. Hornung G, Barziv R, Rosin D, Tokuriki N, Tawfik DS, Oren M, Barkai N (2012) Noise-mean relationship in mutated promoters. Genome Res 22(12):2409–2417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hu J, Chen Z, Xia D, Wu J, Xu H, Ye ZQ (2012) Promoter-associated small double-stranded RNA interacts with heterogeneous nuclear ribonucleoprotein A2/B1 to induce transcriptional activation. Biochem J 447(3):407–416

    Article  CAS  PubMed  Google Scholar 

  8. Huang V, Qin Y, Wang J, Wang X, Place RF, Lin G, Lue TF, Li LC (2010) RNAa is conserved in mammalian cells. PLoS One 5(1):e8848

    Article  PubMed  PubMed Central  Google Scholar 

  9. Janowski BA, Younger ST, Hardy DB, Ram R, Huffman KE, Corey DR (2007) Activating gene expression in mammalian cells with promoter-targeted duplex RNAs. Nat Chem Biol 3(3):166–173

    Article  CAS  PubMed  Google Scholar 

  10. Kharchenko PV, Woo CJ, Tolstorukov MY et al (2008) Nucleosome positioning in human HOX gene clusters. Genome Res 18(10):1554–1561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kuwabara T, Hsieh J, Nakashima K, Taira K, Gage FH (2004) A small modulatory dsRNA specifies the fate of adult neural stem cells. Cell 116(6):779–793

    Article  CAS  PubMed  Google Scholar 

  12. Li LC, Okino ST, Zhao H, Pookot D, Place RF, Urakami S, Enokida H, Dahiya R (2006) Small dsRNAs induce transcriptional activation in human cells. Proc Natl Acad Sci U S A 103(46):17337–17342. doi:0607015103 [pii]10.1073/pnas.0607015103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lin JC, Jeong S, Liang G, Takai D, Fatemi M, Tsai YC, Egger G, Gal-Yam EN, Jones PA (2007) Role of nucleosomal occupancy in the epigenetic silencing of the MLH1 CpG island. Cancer Cell 12(5):432–444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lu B, Morozov AV (2011) Gene regulation by nucleosome positioning. Trends Genet 26(11):476–483

    Google Scholar 

  15. Mahajan MC, Weissman SM (2005) Heterogeneous nuclear ribonucleoprotein C1/C2, MeCP1, and SWI/SNF form a chromatin remodeling complex at the -globin locus control region. Proc Natl Acad Sci U S A 102(42):15012–15017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Place RF, Li LC, Pookot D, Noonan EJ, Dahiya R (2008) MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc Natl Acad Sci U S A 105(5):1608–1613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Portnoy V, Huang V, Place RF, Li LC (2011) Small RNA and transcriptional upregulation. Wiley Interdisciplinary Rev-RNA 2(5):748–760

    Article  CAS  Google Scholar 

  18. Saito Y, Saito H, Liang G, Friedman JM (2014) Epigenetic alterations and microRNA misexpression in cancer and autoimmune diseases: a critical review. Clin Rev Allergy Immunol 47(2):128–135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sandelin A, Carninci P, Lenhard B, Ponjavic J, Hayashizaki Y, Hume DA (2007) Mammalian RNA polymerase II core promoters: insights from genome-wide studies. Nat Rev Genet 8(6):424–436

    Article  CAS  PubMed  Google Scholar 

  20. Vavouri T, Lehner B (2012) Human genes with CpG island promoters have a distinct transcription-associated chromatin organization. Genome Biol 13(11):212–220

    Article  Google Scholar 

  21. Wang B, Sun J, Shi J, Guo Q, Tong X, Zhang J, Hu N, Hu Y (2016) Small-activating RNA can change nucleosome positioning in human fibroblasts. J Biomol Screen 21(6):634–642

    Article  CAS  PubMed  Google Scholar 

  22. Yang C, Bolotin E, Jiang T, Sladek FM, Martinez E (2007) Prevalence of the initiator over the TATA box in human and yeast genes and identification of DNA motifs enriched in human TATA-less core promoters. Gene 389(1):52–65. doi:S0378-1119(06)00623-8 [pii]10.1016/j.gene.2006.09.029

    Article  CAS  PubMed  Google Scholar 

  23. Zhang LT, Wang YG, Liu XY (2008) RNAa: a new contra-standard model for ncRNA regulating gene expression. Chinese J Cell Biol 30(3):281–286

    Google Scholar 

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Correspondence to Yunzhang Hu .

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Wang, B., Hu, Y. (2017). Promoter-Targeted Small Activating RNAs Alter Nucleosome Positioning. In: Li, LC. (eds) RNA Activation. Advances in Experimental Medicine and Biology, vol 983. Springer, Singapore. https://doi.org/10.1007/978-981-10-4310-9_4

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