transcriptional silencer elements


Summary: Nucleic acid sequences that are involved in the negative regulation of GENETIC TRANSCRIPTION by chromatin silencing.

Top Publications

  1. Kemp D, Lin J, Ubeda M, Habener J. NRSF/REST confers transcriptional repression of the GPR10 gene via a putative NRSE/RE-1 located in the 5' promoter region. FEBS Lett. 2002;531:193-8 pubmed
    ..In conclusion, we demonstrate that the GPR10 gene is specifically regulated by NRSF, and suggest this to be a contributory factor in the tissue-specific distribution of GPR10 in vivo. ..
  2. Chasin L. Searching for splicing motifs. Adv Exp Med Biol. 2007;623:85-106 pubmed
    ..A present challenge lies in understanding how the cell integrates this surfeit of information to generate what is usually a binary splicing decision. ..
  3. Kashima T, Manley J. A negative element in SMN2 exon 7 inhibits splicing in spinal muscular atrophy. Nat Genet. 2003;34:460-3 pubmed
    ..Our findings not only define a new mechanism underlying the inefficient splicing of SMN2 exon 7 but also illustrate more generally the remarkable sensitivity and precision that characterizes control of mRNA splicing. ..
  4. Zhang X, Chasin L. Computational definition of sequence motifs governing constitutive exon splicing. Genes Dev. 2004;18:1241-50 pubmed
    ..The large number of effective sequences implied by these results suggests that sequences that influence splicing may be very abundant in pre-mRNA. ..
  5. Nielsen K, Sørensen S, Cartegni L, Corydon T, Doktor T, Schroeder L, et al. Seemingly neutral polymorphic variants may confer immunity to splicing-inactivating mutations: a synonymous SNP in exon 5 of MCAD protects from deleterious mutations in a flanking exonic splicing enhancer. Am J Hum Genet. 2007;80:416-32 pubmed
  6. Uvarov P, Pruunsild P, Timmusk T, Airaksinen M. Neuronal K+/Cl- co-transporter (KCC2) transgenes lacking neurone restrictive silencer element recapitulate CNS neurone-specific expression and developmental up-regulation of endogenous KCC2 gene. J Neurochem. 2005;95:1144-55 pubmed
    ..Thus, developmental up-regulation of the KCC2 gene does not require NRSE(KCC2) and the 1.4-kb KCC2 promoter is largely sufficient for neurone-specific expression of KCC2. ..
  7. Wang Z, Xiao X, Van Nostrand E, Burge C. General and specific functions of exonic splicing silencers in splicing control. Mol Cell. 2006;23:61-70 pubmed
    ..Together, our findings provide a comprehensive picture of the functions of ESSs in the control of diverse types of splicing decisions. ..
  8. Partridge J, Scott K, Bannister A, Kouzarides T, Allshire R. cis-acting DNA from fission yeast centromeres mediates histone H3 methylation and recruitment of silencing factors and cohesin to an ectopic site. Curr Biol. 2002;12:1652-60 pubmed
    ..Recruitment of Rad21-cohesin underscores the link between heterochromatin and chromatid cohesion and indicates that these centromeric elements act independently of kinetochore activity to recruit cohesin. ..
  9. Sironi M, Menozzi G, Riva L, Cagliani R, Comi G, Bresolin N, et al. Silencer elements as possible inhibitors of pseudoexon splicing. Nucleic Acids Res. 2004;32:1783-91 pubmed

More Information


  1. Pozzoli U, Sironi M. Silencers regulate both constitutive and alternative splicing events in mammals. Cell Mol Life Sci. 2005;62:1579-604 pubmed
    ..These methods and are briefly described, as well as the motifs they retrieved, and summary of silenced exons is provided. ..
  2. Wang Z, Rolish M, Yeo G, Tung V, Mawson M, Burge C. Systematic identification and analysis of exonic splicing silencers. Cell. 2004;119:831-45 pubmed
    ..ExonScan and related bioinformatic analyses suggest that these ESS motifs play important roles in suppression of pseudoexons, in splice site definition, and in AS. ..
  3. Singh N, Singh N, Androphy E, Singh R. Splicing of a critical exon of human Survival Motor Neuron is regulated by a unique silencer element located in the last intron. Mol Cell Biol. 2006;26:1333-46 pubmed
  4. Hiller M, Zhang Z, Backofen R, Stamm S. Pre-mRNA secondary structures influence exon recognition. PLoS Genet. 2007;3:e204 pubmed
    ..Our results explain the action of mutations that affect splicing and indicate that the structural context of splicing motifs is part of the mRNA splicing code. ..
  5. Wang Z, Burge C. Splicing regulation: from a parts list of regulatory elements to an integrated splicing code. RNA. 2008;14:802-13 pubmed publisher
    ..Here, we summarize the current state of knowledge of splicing cis-regulatory elements and their context-dependent effects on splicing, emphasizing recent global/genome-wide studies and open questions. ..
  6. Li Z, Pogany J, Panavas T, Xu K, Esposito A, Kinzy T, et al. Translation elongation factor 1A is a component of the tombusvirus replicase complex and affects the stability of the p33 replication co-factor. Virology. 2009;385:245-60 pubmed publisher
    ..We also demonstrate binding of eEF1A to the p33 replication protein and a known cis-acting element at the 3' end of TBSV RNA. Using a functional mutant of eEF1A, we provide evidence on the involvement of eEF1A in TBSV replication...
  7. Kwak I, Song S, Blum J, Simmen R, Simmen F. Enhancer- and silencer-like sequences that mediate insulin-like growth factor-binding protein-2 gene expression in uterine cells of pregnancy. DNA Cell Biol. 2006;25:6-18 pubmed
    ..Results identify novel DNA motifs that regulate the IGFBP-2 gene promoter in uterine endometrium in pregnancy-associated fashion. ..
  8. Chan P, Ma E, Philipsen S, Tan Un K. The study of sequence configuration and functional impact of the (AC)n(AT)xTy motif in human beta-globin gene promoter. Am J Hematol. 2007;82:342-8 pubmed
    ..Am J Hematol 1991;36:42-47). We postulate that silencer elements in the beta-globin promoter play an important role in modifying the clinical presentation of the disease. ..
  9. Braidotti G, Baubec T, Pauler F, Seidl C, Smrzka O, Stricker S, et al. The Air noncoding RNA: an imprinted cis-silencing transcript. Cold Spring Harb Symp Quant Biol. 2004;69:55-66 pubmed
  10. Matsui H, Shinjyo T, Inaba T. Structure of the human Bim gene and its transcriptional regulation in Baf-3, interleukin-3-dependent hematopoietic cells. Mol Biol Rep. 2005;32:79-85 pubmed
  11. Strom A, Forsgren L, Holmberg M. A role for both wild-type and expanded ataxin-7 in transcriptional regulation. Neurobiol Dis. 2005;20:646-55 pubmed
    ..The repression could be counteracted by inhibition of deacetylation, suggesting that ataxin-7 may act as a repressor of transcription by inhibiting the acetylation activity of TFTC and STAGA. ..
  12. Mok H, Lever A. Waking up the sleepers: HIV latency and reactivation. J Formos Med Assoc. 2008;107:909-14 pubmed publisher
    ..This article reviews the research and clinical findings and discusses current thinking on the subject of HIV latency and reactivation. ..
  13. Imaizumi K. [Molecular mechanisms in aberrant splicing in neurological disorders]. Tanpakushitsu Kakusan Koso. 2005;50:330-42 pubmed
  14. Weiss A, Charbonnier E, Ellertsdottir E, Tsirigos A, Wolf C, Schuh R, et al. A conserved activation element in BMP signaling during Drosophila development. Nat Struct Mol Biol. 2010;17:69-76 pubmed publisher
    ..The AE allows the identification of hitherto unknown direct Dpp targets and is functionally conserved in vertebrates. ..
  15. Pidoux A, Richardson W, Allshire R. Sim4: a novel fission yeast kinetochore protein required for centromeric silencing and chromosome segregation. J Cell Biol. 2003;161:295-307 pubmed
    ..Our analyses illustrate the fundamental link between silencing, chromatin structure, and kinetochore function, and establish defective silencing as a powerful approach for identifying proteins required to build a functional kinetochore. ..
  16. Cohen S, Brylawski B, Cordeiro Stone M, Kaufman D. Same origins of DNA replication function on the active and inactive human X chromosomes. J Cell Biochem. 2003;88:923-31 pubmed
    ..Therefore, transcription activity at the HPRT and G6PD genes is not necessary for initiation of DNA replication at the origins mapped to these chromosomal loci. ..
  17. Zuccato C, Tartari M, Crotti A, Goffredo D, Valenza M, Conti L, et al. Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nat Genet. 2003;35:76-83 pubmed
    ..These data identify a new mechanism by which mutation of huntingtin causes loss of transcription of neuronal genes. ..
  18. Nogami H, Hiraoka Y, Ogasawara K, Aiso S, Hisano S. The role of pit-1 in the regulation of the rat growth hormone-releasing hormone receptor gene transcription by glucocorticoids. J Mol Endocrinol. 2005;35:477-88 pubmed
    ..The present results also suggest that the synergistic activation of the rat GHRH-receptor gene transcription depends on the proper distance between the proximal glucocorticoid response element and the pit-1 binding site. ..
  19. Holtz R, Choi J, Petroff M, Piskurich J, Murphy S. Class II transactivator (CIITA) promoter methylation does not correlate with silencing of CIITA transcription in trophoblasts. Biol Reprod. 2003;69:915-24 pubmed
    ..The fact that CIITA is expressed in the stable hybrids implies that trophoblasts may be missing a factor that regulates chromatin structure at the CIITA promoter. ..
  20. Setoguchi R, Tachibana M, Naoe Y, Muroi S, Akiyama K, Tezuka C, et al. Repression of the transcription factor Th-POK by Runx complexes in cytotoxic T cell development. Science. 2008;319:822-5 pubmed publisher
    ..Identification of the transcription factors network in CD4 and CD8 lineage choice provides insight into how distinct T cell subsets are developed for regulating the adaptive immune system. ..
  21. Ou X, Lemonde S, Jafar Nejad H, Bown C, Goto A, Rogaeva A, et al. Freud-1: A neuronal calcium-regulated repressor of the 5-HT1A receptor gene. J Neurosci. 2003;23:7415-25 pubmed
  22. Yaegashi H, Takahashi T, Isogai M, Kobori T, Ohki S, Yoshikawa N. Apple chlorotic leaf spot virus 50 kDa movement protein acts as a suppressor of systemic silencing without interfering with local silencing in Nicotiana benthamiana. J Gen Virol. 2007;88:316-24 pubmed
    ..Collectively, our data indicate that P50 acts as a suppressor of systemic silencing without interfering with local silencing, probably by inhibiting the movement of silencing signals. ..
  23. Verona R, Mann M, Bartolomei M. Genomic imprinting: intricacies of epigenetic regulation in clusters. Annu Rev Cell Dev Biol. 2003;19:237-59 pubmed
    ..These commonalities are reminiscent of the behavior of genes subjected to, and the mechanisms employed in, dosage compensation. ..
  24. Desmet F, Hamroun D, Lalande M, Collod Beroud G, Claustres M, Beroud C. Human Splicing Finder: an online bioinformatics tool to predict splicing signals. Nucleic Acids Res. 2009;37:e67 pubmed publisher
    ..HSF could thus represent a valuable resource for research, diagnostic and therapeutic (e.g. therapeutic exon skipping) purposes as well as for global studies, such as the GEN2PHEN European Project or the Human Variome Project. ..
  25. Lykke Andersen S, Jensen T. CUT it out: silencing of noise in the transcriptome. Nat Struct Mol Biol. 2006;13:860-1 pubmed
  26. Uchikawa J, Shiozawa T, Shih H, Miyamoto T, Feng Y, Kashima H, et al. Expression of steroid receptor coactivators and corepressors in human endometrial hyperplasia and carcinoma with relevance to steroid receptors and Ki-67 expression. Cancer. 2003;98:2207-13 pubmed
    ..Accordingly, limited response to sex steroids in patients with endometrial carcinoma may be ascribed to the dissociation of cofactors and ER/PR. ..
  27. Ivessa A, Lenzmeier B, Bessler J, Goudsouzian L, Schnakenberg S, Zakian V. The Saccharomyces cerevisiae helicase Rrm3p facilitates replication past nonhistone protein-DNA complexes. Mol Cell. 2003;12:1525-36 pubmed
    ..These data indicate that the Rrm3p DNA helicase helps replication forks traverse protein-DNA complexes, naturally occurring impediments that are encountered in each S phase. ..
  28. Miyata A, Sugawara H, Iwata S, Shimizu T, Kangawa K. [The regulatory mechanism for neuron specific expression of PACAP gene]. Nihon Yakurigaku Zasshi. 2004;123:235-42 pubmed
    ..These results suggested that the NRSE-NRSF system might be involved in the regulatory mechanism of neuron-specific expression of the PACAP gene. ..
  29. Malik S, Roeder R. Epigenetics? Mediator does that too!. Mol Cell. 2008;31:305-6 pubmed publisher
    ..2008) report in this issue of Molecular Cell that, by facilitating the recruitment of the G9a methyl transferase, Mediator can also promote epigenetic silencing of selected genes. ..
  30. Azuara Liceaga E, Sandoval M, Corona M, Gariglio P, Lopez Bayghen E. The human involucrin gene is transcriptionally repressed through a tissue-specific silencer element recognized by Oct-2. Biochem Biophys Res Commun. 2004;318:361-71 pubmed
    ..Overexpression of Oct-2 repressed the involucrin promoter activity in epithelial cells and in the presence of the silencer element. ..
  31. Champion M. Gag order. Mol Cell. 2004;14:694-6 pubmed
    ..2004) characterize the order of PcG protein recruitment to specific regions of Ubx and substantiate a binding-in trans looping model of repression that may interfere with transcription initiation or elongation. ..
  32. Schoenfelder S, Paro R. Drosophila Su(Hw) regulates an evolutionarily conserved silencer from the mouse H19 imprinting control region. Cold Spring Harb Symp Quant Biol. 2004;69:47-54 pubmed
  33. Sen S, Talukdar I, Webster N. SRp20 and CUG-BP1 modulate insulin receptor exon 11 alternative splicing. Mol Cell Biol. 2009;29:871-80 pubmed publisher
    ..Thus, we propose that SRp20, SF2/ASF, and CUG-BP1 act antagonistically to regulate IR alternative splicing in vivo and that the relative ratios of SRp20 and SF2/ASF to CUG-BP1 in different cells determine the degree of exon inclusion. ..
  34. Madsen J, Stoltzfus C. An exonic splicing silencer downstream of the 3' splice site A2 is required for efficient human immunodeficiency virus type 1 replication. J Virol. 2005;79:10478-86 pubmed
    ..Either of these changes restored both HIV-1 replication and regulated viral splicing. Therefore, inhibition of HIV-1 3'ss A2 splicing is necessary for HIV-1 replication. ..
  35. Pennisi E. Searching for the genome's second code. Science. 2004;306:632-5 pubmed
  36. Sprowles A, Robinson D, Wu Y, Kung H, Wisdom R. c-Jun controls the efficiency of MAP kinase signaling by transcriptional repression of MAP kinase phosphatases. Exp Cell Res. 2005;308:459-68 pubmed
    ..The results show that one function of c-Jun is to regulate the efficiency of signaling by the ERK, p38, and JNK MAP kinases, a function that is likely to affect cellular responses to many different stimuli. ..
  37. Sonneveld T, Tobutt K, Vaughan S, Robbins T. Loss of pollen-S function in two self-compatible selections of Prunus avium is associated with deletion/mutation of an S haplotype-specific F-box gene. Plant Cell. 2005;17:37-51 pubmed
  38. Kullyev A, Savitskaia E, Georgiev P, Gruzdeva N. [Roles of silencers from the regulatory region of the abdominal-B gene and the Zw5 and Su(Hw) insulators in regulating gene expression in Drosophila melanogaster]. Genetika. 2004;40:1722-5 pubmed
    ..The long-distance interaction between insulators was assumed to depend on the combined effects of silencers, insulators, and, possibly, some unidentified regulatory elements. ..
  39. Wang Y, Wang J, Gao L, Lafyatis R, Stamm S, Andreadis A. Tau exons 2 and 10, which are misregulated in neurodegenerative diseases, are partly regulated by silencers which bind a SRp30c.SRp55 complex that either recruits or antagonizes htra2beta1. J Biol Chem. 2005;280:14230-9 pubmed
    ..This work provides interesting insights into the splicing regulation of the tau gene. ..
  40. Llorian M, Schwartz S, Clark T, Hollander D, Tan L, Spellman R, et al. Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB. Nat Struct Mol Biol. 2010;17:1114-23 pubmed publisher
    ..Our results show that PTB, an archetypal splicing repressor, has variable splicing activity that predictably depends upon its binding location with respect to target exons. ..
  41. Schauer S, Schlüter P, Baskar R, Gheyselinck J, Bolaños A, Curtis M, et al. Intronic regulatory elements determine the divergent expression patterns of AGAMOUS-LIKE6 subfamily members in Arabidopsis. Plant J. 2009;59:987-1000 pubmed publisher
    ..Together, these results suggest that AGL6 and AGL13 show signs of subfunctionalization, with divergent expression patterns, regulatory sequences and possibly functions. ..
  42. Fu T, Li P, Wang H, He Y, Luo D, Zhang A, et al. c-Rel is a transcriptional repressor of EPHB2 in colorectal cancer. J Pathol. 2009;219:103-13 pubmed publisher
    ..We demonstrate for the first time that c-Rel acts as a transcriptional repressor of EPHB2 and plays an active role in EPHB2 down-regulation in colorectal cancers. ..
  43. Heiner M, Hui J, Schreiner S, Hung L, Bindereif A. HnRNP L-mediated regulation of mammalian alternative splicing by interference with splice site recognition. RNA Biol. 2010;7:56-64 pubmed
    ..In sum, our data provide new insights into the mechanisms of how hnRNP L-bound to intronic sites-regulates exon recognition. ..
  44. Dobrowolski S, Andersen H, Doktor T, Andresen B. The phenylalanine hydroxylase c.30C>G synonymous variation (p.G10G) creates a common exonic splicing silencer. Mol Genet Metab. 2010;100:316-23 pubmed publisher
    ..This is particularly important in PAH, since PKU patients harboring such mutations are unlikely to respond to therapy with 6R-tetrahydrobiopterin (BH(4)), despite the fact that the genetic code indicates otherwise. ..
  45. Tan Y, Li S, Jiang X, Loh W, Foo Y, Loh C, et al. Regulation of protocadherin gene expression by multiple neuron-restrictive silencer elements scattered in the gene cluster. Nucleic Acids Res. 2010;38:4985-97 pubmed publisher
    ..Taken together, our data suggest that the neuronal specificity of protocadherin cluster genes in vertebrates is regulated by the NRSE-NRSF/REST system. ..
  46. Nakano M, Cardinale S, Noskov V, Gassmann R, Vagnarelli P, Kandels Lewis S, et al. Inactivation of a human kinetochore by specific targeting of chromatin modifiers. Dev Cell. 2008;14:507-22 pubmed publisher
    ..Our results reveal that a dynamic balance between centromeric chromatin and heterochromatin is essential for vertebrate kinetochore activity. ..
  47. Ferrero I, Mancini S, Grosjean F, Wilson A, Otten L, MacDonald H. TCRgamma silencing during alphabeta T cell development depends upon pre-TCR-induced proliferation. J Immunol. 2006;177:6038-43 pubmed
    ..Collectively our data reveal an important role for pre-TCR induced proliferation in activating the TCRgamma silencer in alphabeta lineage thymocytes, a process that may reinforce alphabeta or gammadelta lineage commitment. ..
  48. Na H, White K. Structure and prevalence of replication silencer-3' terminus RNA interactions in Tombusviridae. Virology. 2006;345:305-16 pubmed
    ..This survey also revealed a significant level of diversity and modularity with respect to RSEs, 3'CSSs and their structural contexts and, moreover, suggests that RSE-3'CSS interactions are prevalent in Tombusviridae and related viruses...
  49. Panaviene Z, Panavas T, Nagy P. Role of an internal and two 3'-terminal RNA elements in assembly of tombusvirus replicase. J Virol. 2005;79:10608-18 pubmed
    ..Altogether, the role of multiple RNA elements in tombusvirus replicase assembly could be an important factor to ensure fidelity of template selection during replication...
  50. Ambrus A, Chen D, Dai J, Jones R, Yang D. Solution structure of the biologically relevant G-quadruplex element in the human c-MYC promoter. Implications for G-quadruplex stabilization. Biochemistry. 2005;44:2048-58 pubmed
  51. Wagner E, Baraniak A, Sessions O, Mauger D, Moskowitz E, Garcia Blanco M. Characterization of the intronic splicing silencers flanking FGFR2 exon IIIb. J Biol Chem. 2005;280:14017-27 pubmed
    ..Our data defined elements of function within the ISSs flanking exon IIIb and suggested that silencing of this exon is mediated by multiple trans-acting factors. ..
  52. Kamat A, Smith M, Shelton J, Richardson J, Mendelson C. Genomic regions that mediate placental cell-specific and developmental regulation of human Cyp19 (aromatase) gene expression in transgenic mice. Endocrinology. 2005;146:2481-8 pubmed
  53. Patrone L, Henson S, Wall R, Malone C. A conserved sequence upstream of the B29 (Ig beta, CD79b) gene interacts with YY1. Mol Biol Rep. 2004;31:1-11 pubmed
    ..Thus, the BCS may function as a tissue-specific LCR or position-dependent insulator specifically countering the influences of the 5' GH LCR and controlling B29 gene expression. ..