insulator elements


Summary: Nucleic acid regulatory sequences that limit or oppose the action of ENHANCER ELEMENTS and define the boundary between differentially regulated gene loci.

Top Publications

  1. Xi H, Shulha H, Lin J, Vales T, Fu Y, Bodine D, et al. Identification and characterization of cell type-specific and ubiquitous chromatin regulatory structures in the human genome. PLoS Genet. 2007;3:e136 pubmed
    ..Surprisingly, nearly all of these ubiquitous DNaseI HS sites correspond to either promoters or insulator elements: 86% of them are located near annotated transcription start sites and 10% are bound by CTCF, a protein with ..
  2. Ishihara K, Oshimura M, Nakao M. CTCF-dependent chromatin insulator is linked to epigenetic remodeling. Mol Cell. 2006;23:733-42 pubmed
    ..These findings provide insight into the role of CTCF-CHD8 complex in insulation and epigenetic regulation at active insulator sites. ..
  3. Li C, Xiong D, Stamatoyannopoulos G, Emery D. Genomic and functional assays demonstrate reduced gammaretroviral vector genotoxicity associated with use of the cHS4 chromatin insulator. Mol Ther. 2009;17:716-24 pubmed publisher
  4. Ottaviani A, Rival Gervier S, Boussouar A, Foerster A, Rondier D, Sacconi S, et al. The D4Z4 macrosatellite repeat acts as a CTCF and A-type lamins-dependent insulator in facio-scapulo-humeral dystrophy. PLoS Genet. 2009;5:e1000394 pubmed publisher
    ..We propose that contraction of the D4Z4 array contributes to FSHD physio-pathology by acting as a CTCF-dependent insulator in patients. ..
  5. Holohan E, Kwong C, Adryan B, Bartkuhn M, Herold M, Renkawitz R, et al. CTCF genomic binding sites in Drosophila and the organisation of the bithorax complex. PLoS Genet. 2007;3:e112 pubmed
    ..CTCF binding sites identified in the BX-C map precisely to the known insulator elements Mcp, Fab-6, and Fab-8...
  6. Dorman E, Bushey A, Corces V. The role of insulator elements in large-scale chromatin structure in interphase. Semin Cell Dev Biol. 2007;18:682-90 pubmed
    b>Insulator elements can be classified as enhancer-blocking or barrier insulators depending on whether they interfere with enhancer-promoter interactions or act as barriers against the spreading of heterochromatin...
  7. Golovnin A, Melnikova L, Volkov I, Kostuchenko M, Galkin A, Georgiev P. 'Insulator bodies' are aggregates of proteins but not of insulators. EMBO Rep. 2008;9:440-5 pubmed publisher
    ..Hence, it is not the functional genomic insulators but rather aggregated proteins that make the so-called 'insulator bodies'. ..
  8. Engel N, Raval A, Thorvaldsen J, Bartolomei S. Three-dimensional conformation at the H19/Igf2 locus supports a model of enhancer tracking. Hum Mol Genet. 2008;17:3021-9 pubmed publisher
    ..We suggest that enhancers track along the chromosome until they find a suitable promoter sequence to interact with and that insulator elements block further tracking of enhancers.
  9. Simms T, Dugas S, Gremillion J, Ibos M, Dandurand M, Toliver T, et al. TFIIIC binding sites function as both heterochromatin barriers and chromatin insulators in Saccharomyces cerevisiae. Eukaryot Cell. 2008;7:2078-86 pubmed publisher
    ..The results are discussed in the context of how the TFIIIC transcription factor complex may function to demarcate chromosomal domains in yeast and possibly in other eukaryotes. ..

More Information


  1. Ramezani A, Hawley T, Hawley R. Performance- and safety-enhanced lentiviral vectors containing the human interferon-beta scaffold attachment region and the chicken beta-globin insulator. Blood. 2003;101:4717-24 pubmed
  2. Hou C, Zhao H, Tanimoto K, Dean A. CTCF-dependent enhancer-blocking by alternative chromatin loop formation. Proc Natl Acad Sci U S A. 2008;105:20398-403 pubmed publisher
    ..Both enhancer-blocking and insulator-loop formation depend on an intact CTCF site in ectopic HS5 and are sensitive to knock-down of the CTCF protein by siRNA. Thus, intrinsic looping activity of CTCF sites can nullify LCR function. ..
  3. Cuddapah S, Jothi R, Schones D, Roh T, Cui K, Zhao K. Global analysis of the insulator binding protein CTCF in chromatin barrier regions reveals demarcation of active and repressive domains. Genome Res. 2009;19:24-32 pubmed publisher
    ..Our data indicate that CTCF may play important roles in the barrier activity of insulators, and this study provides a resource for further investigation of the CTCF function in organizing chromatin in the human genome. ..
  4. Jiang N, Emberly E, Cuvier O, Hart C. Genome-wide mapping of boundary element-associated factor (BEAF) binding sites in Drosophila melanogaster links BEAF to transcription. Mol Cell Biol. 2009;29:3556-68 pubmed publisher
    b>Insulator elements play a role in gene regulation that is potentially linked to nuclear organization. Boundary element-associated factors (BEAFs) 32A and 32B associate with hundreds of sites on Drosophila polytene chromosomes...
  5. Dhillon N, Raab J, Guzzo J, Szyjka S, Gangadharan S, Aparicio O, et al. DNA polymerase epsilon, acetylases and remodellers cooperate to form a specialized chromatin structure at a tRNA insulator. EMBO J. 2009;28:2583-600 pubmed publisher
    ..Robust insulation during growth and cell division involves the formation of a hypersensitive site at the insulator during chromatin maturation together with competition between acetylases and deacetylases. ..
  6. Wallace H, Plata M, Kang H, Ross M, Labrador M. Chromatin insulators specifically associate with different levels of higher-order chromatin organization in Drosophila. Chromosoma. 2010;119:177-94 pubmed publisher
  7. Dickson J, Gowher H, Strogantsev R, Gaszner M, Hair A, Felsenfeld G, et al. VEZF1 elements mediate protection from DNA methylation. PLoS Genet. 2010;6:e1000804 pubmed publisher
  8. Raab J, Kamakaka R. Insulators and promoters: closer than we think. Nat Rev Genet. 2010;11:439-46 pubmed publisher
    ..These insights can help to reconcile different models of insulator action. ..
  9. MacArthur C, Xue H, Van Hoof D, Lieu P, Dudas M, Fontes A, et al. Chromatin insulator elements block transgene silencing in engineered human embryonic stem cell lines at a defined chromosome 13 locus. Stem Cells Dev. 2012;21:191-205 pubmed publisher
    ..To develop an efficient and reliable genetic engineering strategy in hESCs, we used chromatin insulator elements to flank single-copy transgenes and integrated the combined expression constructs via PhiC31/R4 integrase-..
  10. Mukhopadhyay S, Schedl P, Studitsky V, Sengupta A. Theoretical analysis of the role of chromatin interactions in long-range action of enhancers and insulators. Proc Natl Acad Sci U S A. 2011;108:19919-24 pubmed publisher
  11. Yang J, Corces V. Insulators, long-range interactions, and genome function. Curr Opin Genet Dev. 2012;22:86-92 pubmed publisher
    ..Here we provide an overview of new evidence that has uncovered a wide range of functions for these sequences in addition to their two classical roles. ..
  12. Yajima M, Fairbrother W, Wessel G. ISWI contributes to ArsI insulator function in development of the sea urchin. Development. 2012;139:3613-22 pubmed publisher
    ..These studies reveal a mechanistic basis for ArsI function in the gene regulatory network of early development...
  13. Blanton J, Gaszner M, Schedl P. Protein:protein interactions and the pairing of boundary elements in vivo. Genes Dev. 2003;17:664-75 pubmed
    ..Moreover, consistent with idea that this protein:protein interaction might facilitate pairing of boundary elements, we find that that scs and scs' are in close proximity to each other in Drosophila nuclei. ..
  14. Melnikova L, Juge F, Gruzdeva N, Mazur A, Cavalli G, Georgiev P. Interaction between the GAGA factor and Mod(mdg4) proteins promotes insulator bypass in Drosophila. Proc Natl Acad Sci U S A. 2004;101:14806-11 pubmed
    ..Our data provide direct evidence that heterologous insulators can be bypassed by distal enhancers and identify the interaction between GAF and Mod(mdg4) as a possible means to regulate insulator activity. ..
  15. Akbari O, Bousum A, Bae E, Drewell R. Unraveling cis-regulatory mechanisms at the abdominal-A and Abdominal-B genes in the Drosophila bithorax complex. Dev Biol. 2006;293:294-304 pubmed
    ..The hope is that these studies of gene regulation at the BX-C in the humble fruit fly will provide clues as to how vast intergenic regions contribute to the incredible complexity of gene regulation in other species, including humans. ..
  16. Ryu B, Persons D, Evans Galea M, Gray J, Nienhuis A. A chromatin insulator blocks interactions between globin regulatory elements and cellular promoters in erythroid cells. Blood Cells Mol Dis. 2007;39:221-8 pubmed
    ..Promoter activation in K562 cells by vectors containing globin regulatory elements was significantly reduced by addition of flanking insulator elements.
  17. Gruzdeva N, Kyrchanova O, Parshikov A, Kullyev A, Georgiev P. The Mcp element from the bithorax complex contains an insulator that is capable of pairwise interactions and can facilitate enhancer-promoter communication. Mol Cell Biol. 2005;25:3682-9 pubmed
  18. Gurudatta B, Corces V. Chromatin insulators: lessons from the fly. Brief Funct Genomic Proteomic. 2009;8:276-82 pubmed publisher
    ..Current results suggest that insulators set up cell-specific blueprints of nuclear organization that may contribute to the establishment of different patterns of gene expression during cell differentiation and development. ..
  19. Barkess G, West A. Chromatin insulator elements: establishing barriers to set heterochromatin boundaries. Epigenomics. 2012;4:67-80 pubmed publisher
    ..There is good evidence that barrier elements in vertebrates can form repressive chromatin domain boundaries. Future studies will determine whether barriers are frequently used to define repressive domain boundaries in vertebrates. ..
  20. Byrd K, Corces V. Visualization of chromatin domains created by the gypsy insulator of Drosophila. J Cell Biol. 2003;162:565-74 pubmed
    ..These results suggest that the gypsy insulator might establish higher-order domains of chromatin structure and regulate nuclear organization by tethering the DNA to the nuclear matrix and creating chromatin loops. ..
  21. Roman A, González Rico F, Moltó E, Hernando H, Neto A, Vicente Garcia C, et al. Dioxin receptor and SLUG transcription factors regulate the insulator activity of B1 SINE retrotransposons via an RNA polymerase switch. Genome Res. 2011;21:422-32 pubmed publisher
    ..Hence, B1 SINE retrotransposons represent genome-wide insulators activated by transcription factors that respond to developmental, oncogenic, or toxicological stimuli. ..
  22. Sultana H, Verma S, Mishra R. A BEAF dependent chromatin domain boundary separates myoglianin and eyeless genes of Drosophila melanogaster. Nucleic Acids Res. 2011;39:3543-57 pubmed publisher
    ..We also report that BEAF and GAF are the two major proteins responsible for the ME boundary function. Our studies demonstrate a rational approach to search for potential boundaries in genomic regions that are well annotated. ..
  23. Aker M, Bomsztyk K, Emery D. Poly(ADP-ribose) polymerase-1 (PARP-1) contributes to the barrier function of a vertebrate chromatin insulator. J Biol Chem. 2010;285:37589-97 pubmed publisher
    ..Taken together, this study demonstrates that binding of PARP-1 plays a key functional role in the barrier activity of the extended cHS4 insulator core element. ..
  24. Engel N, Bartolomei M. Mechanisms of insulator function in gene regulation and genomic imprinting. Int Rev Cytol. 2003;232:89-127 pubmed
    ..This review focuses on the roles that insulators have in vivo and reviews models of insulator mechanisms in the light of current understanding of gene regulation. ..
  25. Kirkland J, Kamakaka R. tRNA insulator function: insight into inheritance of transcription states?. Epigenetics. 2010;5:96-9 pubmed
  26. Schoborg T, Labrador M. The phylogenetic distribution of non-CTCF insulator proteins is limited to insects and reveals that BEAF-32 is Drosophila lineage specific. J Mol Evol. 2010;70:74-84 pubmed publisher
  27. Bushey A, Ramos E, Corces V. Three subclasses of a Drosophila insulator show distinct and cell type-specific genomic distributions. Genes Dev. 2009;23:1338-50 pubmed publisher
    ..These findings suggest a model in which insulator subclasses may have distinct functions that together organize the genome in a cell type-specific manner, resulting in differential regulation of gene expression. ..
  28. D Apolito D, Baiamonte E, Bagliesi M, Di Marzo R, Calzolari R, Ferro L, et al. The sea urchin sns5 insulator protects retroviral vectors from chromosomal position effects by maintaining active chromatin structure. Mol Ther. 2009;17:1434-41 pubmed publisher
  29. Xie X, Mikkelsen T, Gnirke A, Lindblad Toh K, Kellis M, Lander E. Systematic discovery of regulatory motifs in conserved regions of the human genome, including thousands of CTCF insulator sites. Proc Natl Acad Sci U S A. 2007;104:7145-50 pubmed
    ..These sites may thus partition the human genome into domains of expression. ..
  30. Hino S, Akasaka K, Matsuoka M. Sea urchin arylsulfatase insulator exerts its anti-silencing effect without interacting with the nuclear matrix. J Mol Biol. 2006;357:18-27 pubmed
  31. Golovnin A, Mazur A, Kopantseva M, Kurshakova M, Gulak P, Gilmore B, et al. Integrity of the Mod(mdg4)-67.2 BTB domain is critical to insulator function in Drosophila melanogaster. Mol Cell Biol. 2007;27:963-74 pubmed
    ..2 BTB domain with the GAF BTB domain produced a nonfunctional protein. Taken together, these data suggest that the Mod(mdg4)-67.2 BTB domain confers novel activities to gypsy insulator function. ..
  32. Ciavatta D, Rogers S, Magnuson T. Drosophila CTCF is required for Fab-8 enhancer blocking activity in S2 cells. J Mol Biol. 2007;373:233-9 pubmed
    ..Furthermore, knockdown of Drosophila CTCF by RNAi in our stable cell lines demonstrates that CTCF itself is critical for Fab-8 enhancer blocking. ..
  33. Wallace J, Felsenfeld G. We gather together: insulators and genome organization. Curr Opin Genet Dev. 2007;17:400-7 pubmed
    ..The properties of CTCF, and its newly described genomic distribution, suggest that it may play an important role in large-scale nuclear architecture, perhaps mediated by the co-factors with which it interacts in vivo. ..
  34. Kuhn Parnell E, Helou C, Marion D, Gilmore B, Parnell T, Wold M, et al. Investigation of the properties of non-gypsy suppressor of hairy-wing-binding sites. Genetics. 2008;179:1263-73 pubmed publisher
    ..These studies extend our understanding of the properties of Su(Hw) and the endogenous genomic regions to which this protein localizes. ..
  35. Yoon Y, Jeong S, Rong Q, Park K, Chung J, Pfeifer K. Analysis of the H19ICR insulator. Mol Cell Biol. 2007;27:3499-510 pubmed
    ..Instead, the ICR insulator forms novel loop domains by associating with the blocked promoters and enhancers. We propose that these associations are fundamental to insulator function. ..
  36. Zhu X, Ling J, Zhang L, Pi W, Wu M, Tuan D. A facilitated tracking and transcription mechanism of long-range enhancer function. Nucleic Acids Res. 2007;35:5532-44 pubmed
  37. Kuhn E, Geyer P. Genomic insulators: connecting properties to mechanism. Curr Opin Cell Biol. 2003;15:259-65 pubmed
    ..Understanding these processes will provide insights into prevention of inappropriate regulatory interactions, knowledge that can be applied to gene therapies. ..
  38. Erokhin M, Davydova A, Kyrchanova O, Parshikov A, Georgiev P, Chetverina D. Insulators form gene loops by interacting with promoters in Drosophila. Development. 2011;138:4097-106 pubmed publisher
    ..Both insulators support basal activity of the yellow and white promoters in eyes. Thus, the ability of insulators to interact with promoters might play an important role in the regulation of basal gene transcription...
  39. Kim T, Abdullaev Z, Smith A, Ching K, Loukinov D, Green R, et al. Analysis of the vertebrate insulator protein CTCF-binding sites in the human genome. Cell. 2007;128:1231-45 pubmed
    b>Insulator elements affect gene expression by preventing the spread of heterochromatin and restricting transcriptional enhancers from activation of unrelated promoters...
  40. Lee D, Singh P, Tsark W, SZABO P. Complete biallelic insulation at the H19/Igf2 imprinting control region position results in fetal growth retardation and perinatal lethality. PLoS ONE. 2010;5:e12630 pubmed publisher
    ..Importantly, late fetal/perinatal death occurred arguing that strict biallelic insulation at the H19/Igf2 ICR position is not tolerated in development. ..
  41. Negre N, Brown C, Shah P, Kheradpour P, Morrison C, Henikoff J, et al. A comprehensive map of insulator elements for the Drosophila genome. PLoS Genet. 2010;6:e1000814 pubmed publisher
    ..proteins-dCTCF, CP190, BEAF-32, Su(Hw), Mod(mdg4), and GAF-to obtain the first comprehensive map of insulator elements in Drosophila embryos...
  42. Valadez Graham V, Razin S, Recillas Targa F. CTCF-dependent enhancer blockers at the upstream region of the chicken alpha-globin gene domain. Nucleic Acids Res. 2004;32:1354-62 pubmed
    ..The results are discussed with respect to special features of the tissue-specific alpha-globin gene domain located in a permanently open chromatin area. ..
  43. Han L, SZABO P, Mann J. Postnatal survival of mice with maternal duplication of distal chromosome 7 induced by a Igf2/H19 imprinting control region lacking insulator function. PLoS Genet. 2010;6:e1000803 pubmed publisher
    ..Our results are consistent with the idea that reduced expression of IGF2 plays a role in the aetiology of the human imprinting-related growth-deficit disorder, Silver-Russell syndrome. ..
  44. Kyrchanova O, Toshchakov S, Parshikov A, Georgiev P. Study of the functional interaction between Mcp insulators from the Drosophila bithorax complex: effects of insulator pairing on enhancer-promoter communication. Mol Cell Biol. 2007;27:3035-43 pubmed
    ..These results indicate that the relative placement and orientation of insulator-like elements can determine proper enhancer-promoter communication. ..
  45. Cavalieri V, Melfi R, Spinelli G. Promoter activity of the sea urchin (Paracentrotus lividus) nucleosomal H3 and H2A and linker H1 {alpha}-histone genes is modulated by enhancer and chromatin insulator. Nucleic Acids Res. 2009;37:7407-15 pubmed publisher
    ..In addition, they suggest that both the H2A enhancer and the sns5 insulator may account for the diverse accumulation of the linker H1 versus the core nucleosomal histones during early development of the sea urchin embryo...
  46. Li M, Belozerov V, Cai H. Analysis of chromatin boundary activity in Drosophila cells. BMC Mol Biol. 2008;9:109 pubmed publisher
    ..It provides a useful tool that complements the transgenic and genetic approaches for studying this important class of regulatory elements. ..
  47. Wei G, Liu D, Liang C. Chromatin domain boundaries: insulators and beyond. Cell Res. 2005;15:292-300 pubmed
    ..In this review, we will discuss recent progress in the field of chromatin domain boundaries. ..
  48. Capelson M, Corces V. The ubiquitin ligase dTopors directs the nuclear organization of a chromatin insulator. Mol Cell. 2005;20:105-16 pubmed
    ..Thus, dTopors appears to be involved in the establishment of chromatin organization through its ability to mediate the association of insulator complexes with a fixed nuclear substrate. ..
  49. Zhao H, Dean A. Organizing the genome: enhancers and insulators. Biochem Cell Biol. 2005;83:516-24 pubmed
    ..Novel experimental approaches are helping to reveal the mechanisms underlying nuclear organization of developmentally regulated genes. ..
  50. Comet I, Schuettengruber B, Sexton T, Cavalli G. A chromatin insulator driving three-dimensional Polycomb response element (PRE) contacts and Polycomb association with the chromatin fiber. Proc Natl Acad Sci U S A. 2011;108:2294-9 pubmed publisher
    ..b>Insulator elements have been proposed to modulate the communication between regulatory elements and promoters due to their ..
  51. Wang J, Lunyak V, Jordan I. Genome-wide prediction and analysis of human chromatin boundary elements. Nucleic Acids Res. 2012;40:511-29 pubmed publisher
  52. Bondarenko V, Liu Y, Jiang Y, Studitsky V. Communication over a large distance: enhancers and insulators. Biochem Cell Biol. 2003;81:241-51 pubmed
    ..These new findings help to understand the mechanism of action of the elements that can prevent enhancer-promoter communication (insulators). ..
  53. Bartkuhn M, Straub T, Herold M, Herrmann M, Rathke C, Saumweber H, et al. Active promoters and insulators are marked by the centrosomal protein 190. EMBO J. 2009;28:877-88 pubmed publisher
    ..Loss of either dCTCF or CP190 causes an increase of H3 and H3K27 trimethylation at these sites. Thus, for both types of cis-regulatory elements, domain borders and promoters, the chromatin structure is dependent on CP190. ..