matrix attachment regions


Summary: Regions of the CHROMATIN or DNA that bind to the NUCLEAR MATRIX. They are found in INTERGENIC DNA, especially flanking the 5' ends of genes or clusters of genes. Many of the regions that have been isolated contain a bipartite sequence motif called the MAR/SAR recognition signature sequence that binds to MATRIX ATTACHMENT REGION BINDING PROTEINS.

Top Publications

  1. Heng H, Goetze S, Ye C, Liu G, Stevens J, Bremer S, et al. Chromatin loops are selectively anchored using scaffold/matrix-attachment regions. J Cell Sci. 2004;117:999-1008 pubmed
    ..Consequently, S/MAR anchors were necessary but not sufficient for chromatin loops to form. These observations reconcile many seemingly contradictory attributes previously associated with S/MARs...
  2. Yamasaki K, Akiba T, Yamasaki T, Harata K. Structural basis for recognition of the matrix attachment region of DNA by transcription factor SATB1. Nucleic Acids Res. 2007;35:5073-84 pubmed
    ..expression essential in immune T-cell maturation and switching of fetal globin species, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin remodeling...
  3. Bode J, Goetze S, Heng H, Krawetz S, Benham C. From DNA structure to gene expression: mediators of nuclear compartmentalization and dynamics. Chromosome Res. 2003;11:435-45 pubmed
    ..Recent investigations and novel techniques have shown that these contacts can be altered by modulators as well as by specific interactions with the components of enhancers and locus control regions. ..
  4. Girod P, Nguyen D, Calabrese D, Puttini S, Grandjean M, Martinet D, et al. Genome-wide prediction of matrix attachment regions that increase gene expression in mammalian cells. Nat Methods. 2007;4:747-53 pubmed
    ..Use of epigenetic regulators such as matrix attachment regions (MARs) is a promising approach to alleviate such unwanted effects...
  5. Purbey P, Singh S, Kumar P, Mehta S, Ganesh K, Mitra D, et al. PDZ domain-mediated dimerization and homeodomain-directed specificity are required for high-affinity DNA binding by SATB1. Nucleic Acids Res. 2008;36:2107-22 pubmed publisher
    ..These studies provide mechanistic insights into the mode of DNA binding and its effect on the regulation of transcription by SATB1. ..
  6. Eivazova E, Gavrilov A, Pirozhkova I, Petrov A, Iarovaia O, Razin S, et al. Interaction in vivo between the two matrix attachment regions flanking a single chromatin loop. J Mol Biol. 2009;386:929-37 pubmed publisher
    ..The present findings have important implications in terms of mechanisms of illegitimate recombination that can result in chromosomal translocations and deletions. ..
  7. Galbete J, Buceta M, Mermod N. MAR elements regulate the probability of epigenetic switching between active and inactive gene expression. Mol Biosyst. 2009;5:143-50 pubmed publisher
    ..The MAR thus confers a more deterministic behavior to an otherwise stochastic process, providing a means towards more reliable expression of engineered genetic systems. ..
  8. Wang L, Di L, Lv X, Zheng W, Xue Z, Guo Z, et al. Inter-MAR association contributes to transcriptionally active looping events in human beta-globin gene cluster. PLoS ONE. 2009;4:e4629 pubmed publisher
    b>Matrix attachment regions (MARs) are important in chromatin organization and gene regulation...
  9. Petrova N, Iarovaia O, Verbovoy V, Razin S. Specific radial positions of centromeres of human chromosomes X, 1, and 19 remain unchanged in chromatin-depleted nuclei of primary human fibroblasts: evidence for the organizing role of the nuclear matrix. J Cell Biochem. 2005;96:850-7 pubmed
    ..These results strongly suggest that the characteristic organization of interphase chromosomes is supported by the proteinous nuclear matrix and is not maintained by simple repulsing of negatively charged chromosomes. ..

More Information


  1. Linnemann A, Krawetz S. Silencing by nuclear matrix attachment distinguishes cell-type specificity: association with increased proliferation capacity. Nucleic Acids Res. 2009;37:2779-88 pubmed publisher
  2. Sgourou A, Routledge S, Spathas D, Athanassiadou A, Antoniou M. Physiological levels of HBB transgene expression from S/MAR element-based replicating episomal vectors. J Biotechnol. 2009;143:85-94 pubmed publisher
    ..These data provide the principles upon which generic and flexible expression cassette-S/MAR-based REVs can be designed for a wide range of applications. ..
  3. Girod P, Zahn Zabal M, Mermod N. Use of the chicken lysozyme 5' matrix attachment region to generate high producer CHO cell lines. Biotechnol Bioeng. 2005;91:1-11 pubmed
    ..When used to express immunoglobulins, the S/MAR element enabled cell clones with high and stable levels of expression to be isolated following the analysis of a few cell lines generated without transgene amplification procedures. ..
  4. Wang T, Zhang J, Jing C, Yang X, Lin J. Positional effects of the matrix attachment region on transgene expression in stably transfected CHO cells. Cell Biol Int. 2010;34:141-5 pubmed publisher
    ..We have also shown that the transgene expression level is not directly proportional to the gene copy number, and gene copy number dependency does not exist. ..
  5. Goetze S, Baer A, Winkelmann S, Nehlsen K, Seibler J, Maass K, et al. Performance of genomic bordering elements at predefined genomic loci. Mol Cell Biol. 2005;25:2260-72 pubmed
    ..Insulators and/or scaffold-matrix attachment regions (S/MARs) mark the boundaries of these chromatin domains where they delimit enhancing and silencing ..
  6. Halweg C, Thompson W, Spiker S. The rb7 matrix attachment region increases the likelihood and magnitude of transgene expression in tobacco cells: a flow cytometric study. Plant Cell. 2005;17:418-29 pubmed
    Many studies in both plant and animal systems have shown that matrix attachment regions (MARs) can increase expression of transgenes in whole organisms or cells in culture...
  7. Buceta M, Galbete J, Kostic C, Arsenijevic Y, Mermod N. Use of human MAR elements to improve retroviral vector production. Gene Ther. 2011;18:7-13 pubmed publisher
    ..Thus, use of MAR elements opens new perspectives for the efficient generation of gene therapy vectors. ..
  8. Butaye K, Goderis I, Wouters P, Pues J, Delauré S, Broekaert W, et al. Stable high-level transgene expression in Arabidopsis thaliana using gene silencing mutants and matrix attachment regions. Plant J. 2004;39:440-9 pubmed
    ..We further show that T-DNA constructs flanked by matrix attachment regions of the chicken lysozyme gene (chiMARs) cause a boost in GUS activity by fivefold in sgs2 and 12-fold in ..
  9. Rudd S, Frisch M, Grote K, Meyers B, Mayer K, Werner T. Genome-wide in silico mapping of scaffold/matrix attachment regions in Arabidopsis suggests correlation of intragenic scaffold/matrix attachment regions with gene expression. Plant Physiol. 2004;135:715-22 pubmed
    We carried out a genome-wide prediction of scaffold/matrix attachment regions (S/MARs) in Arabidopsis. Results indicate no uneven distribution on the chromosomal level but a clear underrepresentation of S/MARs inside genes...
  10. Namciu S, Friedman R, Marsden M, Sarausad L, Jasoni C, Fournier R. Sequence organization and matrix attachment regions of the human serine protease inhibitor gene cluster at 14q32.1. Mamm Genome. 2004;15:162-78 pubmed
    ..Several differences between the MAR-Wiz predictions and the results of biochemical tests were observed. The genomic organization of the serpin gene cluster is discussed. ..
  11. Sinha S, Malonia S, Mittal S, Singh K, Kadreppa S, Kamat R, et al. Coordinated regulation of p53 apoptotic targets BAX and PUMA by SMAR1 through an identical MAR element. EMBO J. 2010;29:830-42 pubmed publisher
    ..Thus, our study establishes MAR as a damage responsive cis element and SMAR1-PML crosstalk as a switch that modulates the decision between cell cycle arrest and apoptosis in response to DNA damage. ..
  12. Tachiki K, Kodama Y, Nakayama H, Shinmyo A. Determination of the in vivo distribution of nuclear matrix attachment regions using a polymerase chain reaction-based assay in Arabidopsis thaliana. J Biosci Bioeng. 2009;108:11-9 pubmed publisher
    b>Matrix attachment regions (MARs) are the regions on genomic DNA that are attached to the nuclear matrix in eukaryotes...
  13. Wong S, Argyros O, Coutelle C, Harbottle R. Non-viral S/MAR vectors replicate episomally in vivo when provided with a selective advantage. Gene Ther. 2011;18:82-7 pubmed publisher
    ..These results provide proof-of-principle that S/MAR vectors are capable of preventing transgene silencing, are resistant to integration and are able to confer mitotic stability in vivo when provided with a selective advantage. ..
  14. Hagedorn C, Wong S, Harbottle R, Lipps H. Scaffold/matrix attached region-based nonviral episomal vectors. Hum Gene Ther. 2011;22:915-23 pubmed publisher
    ..These vectors have found broad application in basic research but are now improved for their use in the safe and reproducible genetic modification of cells and organisms and in gene therapy. ..
  15. Grandjean M, Girod P, Calabrese D, Kostyrko K, Wicht M, Yerly F, et al. High-level transgene expression by homologous recombination-mediated gene transfer. Nucleic Acids Res. 2011;39:e104 pubmed publisher
    ..Silencing may be limited by the use of epigenetic regulatory sequences such as matrix attachment regions (MAR)...
  16. Wang F, Wang T, Tang Y, Zhang J, Yang X. Different matrix attachment regions flanking a transgene effectively enhance gene expression in stably transfected Chinese hamster ovary cells. Gene. 2012;500:59-62 pubmed publisher
    Numerous matrix attachment regions (MARs) have been used to improve transgene expression in genetic engineering, but an efficient and stable expression vector is lacking...
  17. Anthony A, Blaxter M. Association of the matrix attachment region recognition signature with coding regions in Caenorhabditis elegans. BMC Genomics. 2007;8:418 pubmed
    b>Matrix attachment regions (MAR) are the sites on genomic DNA that interact with the nuclear matrix. There is increasing evidence for the involvement of MAR in regulation of gene expression...
  18. Wang P, Wang T, Wang Y, Yang R, Li Z. Cloning and genomic nucleotide sequence of the matrix attachment region binding protein from the halotolerant alga Dunaliella salina. J Basic Microbiol. 2013;53:622-9 pubmed publisher
    ..All the introns in the D. salina MBP gene have orthodox splice sites, exhibiting GT at the 5' end and AG at the 3' end. Southern blot analysis showed that MBP only has one copy in the D. salina genome. ..
  19. Kurre P, Morris J, Thomasson B, Kohn D, Kiem H. Scaffold attachment region-containing retrovirus vectors improve long-term proviral expression after transplantation of GFP-modified CD34+ baboon repopulating cells. Blood. 2003;102:3117-9 pubmed
  20. Lufino M, Manservigi R, Wade Martins R. An S/MAR-based infectious episomal genomic DNA expression vector provides long-term regulated functional complementation of LDLR deficiency. Nucleic Acids Res. 2007;35:e98 pubmed
    ..This vector overcomes the major problems of vector integration and unregulated transgene expression. ..
  21. Wang T, Xue L, Hou W, Yang B, Chai Y, Ji X, et al. Increased expression of transgene in stably transformed cells of Dunaliella salina by matrix attachment regions. Appl Microbiol Biotechnol. 2007;76:651-7 pubmed
    Nuclear matrix attachment regions (MARs) are known to bind specifically to the nuclear scaffold and are thought to influence expression of the transgenes...
  22. Kumar P, Bischof O, Purbey P, Notani D, Urlaub H, Dejean A, et al. Functional interaction between PML and SATB1 regulates chromatin-loop architecture and transcription of the MHC class I locus. Nat Cell Biol. 2007;9:45-56 pubmed
    ..Our studies identify PML and SATB1 as a regulatory complex that governs transcription by orchestrating dynamic chromatin-loop architecture. ..
  23. Eivazova E, Vassetzky Y, Aune T. Selective matrix attachment regions in T helper cell subsets support loop conformation in the Ifng gene. Genes Immun. 2007;8:35-43 pubmed
    ..Here, we analyzed nuclear matrix attachment regions (MARs) in the Ifng gene by DNA array technique in unactivated and activated CD4+ Th cells...
  24. Schaarschmidt D, Baltin J, Stehle I, Lipps H, Knippers R. An episomal mammalian replicon: sequence-independent binding of the origin recognition complex. EMBO J. 2004;23:191-201 pubmed
    ..It indicates that specific DNA sequences are not required for the chromatin binding of ORC in vivo. The conclusion is that epigenetic mechanisms determine the sites where mammalian DNA replication is initiated. ..
  25. Platts A, Quayle A, Krawetz S. In-silico prediction and observations of nuclear matrix attachment. Cell Mol Biol Lett. 2006;11:191-213 pubmed
    ..On the one hand, both the reiteration and sequence similarity of some elements of Matrix Attachment Regions suggest conservation. On the other hand, in-silico predictions suggest additional unique components...
  26. Iarovaia O, Shkumatov P, Razin S. Breakpoint cluster regions of the AML-1 and ETO genes contain MAR elements and are preferentially associated with the nuclear matrix in proliferating HEL cells. J Cell Sci. 2004;117:4583-90 pubmed
    ..The data are discussed in the framework of the hypothesis postulating that the nuclear matrix plays an important role in determining the positions of recombination-prone areas. ..
  27. Kim J, Kim J, Park D, Kang H, Yoon J, Baek K, et al. Improved recombinant gene expression in CHO cells using matrix attachment regions. J Biotechnol. 2004;107:95-105 pubmed
    ..This eliminates the need to isolate individual colonies followed by multi-step treatments of methotrexate and thereby greatly simplifies this mammalian expression system. ..
  28. Fiorini A, Gouveia F, Fernandez M. Scaffold/Matrix Attachment Regions and intrinsic DNA curvature. Biochemistry (Mosc). 2006;71:481-8 pubmed
    Recent approaches have failed to detect nucleotide sequence motifs in Scaffold/Matrix Attachment Regions (S/MARs)...
  29. Xie F, Wang X, Cooper D, Chuzhanova N, Fang Y, Cai X, et al. A novel Alu-mediated 61-kb deletion of the von Willebrand factor (VWF) gene whose breakpoints co-locate with putative matrix attachment regions. Blood Cells Mol Dis. 2006;36:385-91 pubmed
    ..then performed to search for repetitive sequence elements, recombination-associated motifs, and scaffold/matrix attachment regions (S/MARs)...
  30. Bode J, Winkelmann S, Götze S, Spiker S, Tsutsui K, Bi C, et al. Correlations between scaffold/matrix attachment region (S/MAR) binding activity and DNA duplex destabilization energy. J Mol Biol. 2006;358:597-613 pubmed
  31. Shimizu N, Hanada N, Utani K, Sekiguchi N. Interconversion of intra- and extra-chromosomal sites of gene amplification by modulation of gene expression and DNA methylation. J Cell Biochem. 2007;102:515-29 pubmed
    ..These results have important implications for both protein production technology, and the generation of chromosomal abnormalities found in human cancer cells. ..
  32. Papapetrou E, Ziros P, Micheva I, Zoumbos N, Athanassiadou A. Gene transfer into human hematopoietic progenitor cells with an episomal vector carrying an S/MAR element. Gene Ther. 2006;13:40-51 pubmed
    ..Recent insights into the ability of chromosomal scaffold/matrix attachment regions (S/MARs) to mediate episomal maintenance of genetic elements allowed the development of a small circular ..
  33. Namciu S, Fournier R. Human matrix attachment regions are necessary for the establishment but not the maintenance of transgene insulation in Drosophila melanogaster. Mol Cell Biol. 2004;24:10236-45 pubmed
    Human matrix attachment regions (MARs) can insulate transgene expression from chromosomal position effects in Drosophila melanogaster...
  34. Koina E, Piper A. An inactive X specific replication origin associated with a matrix attachment region in the human X linked HPRT gene. J Cell Biochem. 2005;95:391-402 pubmed
    ..The origin is located approximately 2 kb upstream of a matrix attachment region (MAR) and also contains two A:T-rich elements, thought to facilitate DNA unwinding. ..
  35. Wang T, Hou G, Wang Y, Xue L. Characterization and heterologous expression of a new matrix attachment region binding protein from the unicellular green alga Dunaliella salina. J Biochem. 2010;148:651-8 pubmed publisher
    Although interactions between the nuclear matrix and special regions of chromosomal DNA called matrix attachment regions (MARs) are implicated in various nuclear functions, the understanding of the regulatory mechanism of MARs is still ..
  36. Harraghy N, Regamey A, Girod P, Mermod N. Identification of a potent MAR element from the mouse genome and assessment of its activity in stable and transient transfections. J Biotechnol. 2011;154:11-20 pubmed publisher
    b>Matrix attachment regions are DNA sequences found throughout eukaryotic genomes that are believed to define boundaries interfacing heterochromatin and euchromatin domains, thereby acting as epigenetic regulators...
  37. Kulkarni A, Pavithra L, Rampalli S, Mogare D, Babu K, Shiekh G, et al. HIV-1 integration sites are flanked by potential MARs that alone can act as promoters. Biochem Biophys Res Commun. 2004;322:672-7 pubmed
    b>Matrix attachment regions (MARs) are cis regulatory elements that modulate gene expression in a tissue and cell stage specific manner. Recent reports show that viral integration within the genome takes place at nonrandom active genes...
  38. Harraghy N, Buceta M, Regamey A, Girod P, Mermod N. Using matrix attachment regions to improve recombinant protein production. Methods Mol Biol. 2012;801:93-110 pubmed publisher
    ..b>Matrix attachment regions (MARs) are DNA sequences that help generate and maintain an open chromatin domain that is favourable to ..
  39. Barboro P, Repaci E, D Arrigo C, Balbi C. The role of nuclear matrix proteins binding to matrix attachment regions (Mars) in prostate cancer cell differentiation. PLoS ONE. 2012;7:e40617 pubmed publisher
    ..The NM interacts with chromatin via specialized DNA sequences called matrix attachment regions (MARs)...
  40. Araki Y, Hamafuji T, Noguchi C, Shimizu N. Efficient recombinant production in mammalian cells using a novel IR/MAR gene amplification method. PLoS ONE. 2012;7:e41787 pubmed publisher
    ..In conclusion, the IR/MAR gene amplification method is a novel and efficient platform for recombinant antibody production in mammalian cells, which rapidly and easily enables the establishment of stable high-producer cell clone. ..
  41. Koirala A, Makkia R, Conley S, Cooper M, Naash M. S/MAR-containing DNA nanoparticles promote persistent RPE gene expression and improvement in RPE65-associated LCA. Hum Mol Genet. 2013;22:1632-42 pubmed publisher
    ..These results indicate that the non-viral delivery of hRPE65 vectors can result in persistent, therapeutically efficacious gene expression in the RPE. ..
  42. Rupprecht S, Hagedorn C, Seruggia D, Magnusson T, Wagner E, Ogris M, et al. Controlled removal of a nonviral episomal vector from transfected cells. Gene. 2010;466:36-42 pubmed publisher
    ..This inducible episomal nonviral vector system will find broad application in gene therapy but also in reprogramming of somatic cells or modification of stem cells. ..
  43. Drennan K, Linnemann A, Platts A, Heng H, Armant D, Krawetz S. Nuclear matrix association: switching to the invasive cytotrophoblast. Placenta. 2010;31:365-72 pubmed publisher
    ..This study supports the view that nuclear matrix attachment may play an important role in cytotrophoblast invasion by ensuring specific silencing that facilitates invasion. ..
  44. Haase R, Argyros O, Wong S, Harbottle R, Lipps H, Ogris M, et al. pEPito: a significantly improved non-viral episomal expression vector for mammalian cells. BMC Biotechnol. 2010;10:20 pubmed publisher
    ..The novel vector pEPito can be considered suitable as an improved vector for biotechnological applications in vitro and for non-viral gene delivery in vivo. ..
  45. Ioudinkova E, Petrov A, Razin S, Vassetzky Y. Mapping long-range chromatin organization within the chicken alpha-globin gene domain using oligonucleotide DNA arrays. Genomics. 2005;85:143-51 pubmed
    ..This may prove useful for mapping chromatin loop positions within the human genome by using a pool of chromatin loop attachment regions as a probe in a hybridization with a DNA chip containing a specific DNA region. ..
  46. Purbowasito W, Suda C, Yokomine T, Zubair M, Sado T, Tsutsui K, et al. Large-scale identification and mapping of nuclear matrix-attachment regions in the distal imprinted domain of mouse chromosome 7. DNA Res. 2004;11:391-407 pubmed
    ..This study presents the first large-scale mapping of MARs in an imprinted domain and provides a platform for understanding the roles of MARs in imprinting. ..
  47. Johnson C, Levy L. Matrix attachment regions as targets for retroviral integration. Virol J. 2005;2:68 pubmed
    ..To study the role of DNA structure in site selection, retroviral integration near matrix attachment regions (MARs) was analyzed for three different groups of retroviruses...
  48. Linnemann A, Platts A, Krawetz S. Differential nuclear scaffold/matrix attachment marks expressed genes. Hum Mol Genet. 2009;18:645-54 pubmed publisher
    ..This may be achieved using scaffold/matrix attachment regions (S/MARs) that establish loop domains...
  49. Harraghy N, Gaussin A, Mermod N. Sustained transgene expression using MAR elements. Curr Gene Ther. 2008;8:353-66 pubmed
    b>Matrix attachment regions (MARs) are DNA sequences that may be involved in anchoring DNA/chromatin to the nuclear matrix and they have been described in both mammalian and plant species...
  50. Argyros O, Wong S, Niceta M, Waddington S, Howe S, Coutelle C, et al. Persistent episomal transgene expression in liver following delivery of a scaffold/matrix attachment region containing non-viral vector. Gene Ther. 2008;15:1593-605 pubmed publisher
    ..We conclude that the combination of a mammalian, tissue-specific promoter with the S/MAR element is sufficient to drive long-term episomal pDNA expression of genes in vivo. ..
  51. Jenke A, Wilhelm A, Orth V, Lipps H, Protzer U, Wirth S. Long-term suppression of hepatitis B virus replication by short hairpin RNA expression using the scaffold/matrix attachment region-based replicating vector system pEPI-1. Antimicrob Agents Chemother. 2008;52:2355-9 pubmed publisher
    ..Due to its unique properties compared to commonly used vectors, it provides an interesting option for the treatment of chronically HBV-infected individuals. ..
  52. Moreira P, Perez Crespo M, Ramirez M, Pozueta J, Montoliu L, Gutierrez Adan A. Effect of transgene concentration, flanking matrix attachment regions, and RecA-coating on the efficiency of mouse transgenesis mediated by intracytoplasmic sperm injection. Biol Reprod. 2007;76:336-43 pubmed
    ..we have evaluated the impact of transgene DNA concentration, transgene flanking with nuclear matrix attachment regions (MARs), and the use of recombinase A (RecA)-coated DNA on the efficiency of mouse transgenesis ..
  53. Shaposhnikov S, Akopov S, Chernov I, Thomsen P, Joergensen C, Collins A, et al. A map of nuclear matrix attachment regions within the breast cancer loss-of-heterozygosity region on human chromosome 16q22.1. Genomics. 2007;89:354-61 pubmed
    ..1, we have identified a significant portion of the scaffold/matrix attachment regions (S/MARs) within this region. Forty independent putative S/MAR elements were assigned within the 16q22...