- Open Access
In-silico prediction and observations of nuclear matrix attachment
Cellular & Molecular Biology Letters volume 11, pages191–213 (2006)
The nuclear matrix is a functionally adaptive structural framework interior to the nuclear envelope. The nature and function of this nuclear organizer remains the subject of widespread discussion in the epigenetic literature. To draw this discussion together with a view to suggest a way forward we summarize the biochemical evidence for the modalities of DNA-matrix binding alongside the in-silico predictions. Concordance is exhibited at various, but not all levels. 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. In bringing together biological and sequence evidence we conclude that binding may be hierarchical in nature, reflective of a biological role in replicating, transcribing and potentiating chromatin. Nuclear matrix binding may well be more complex than the widely accepted simple loop model.
a linear discriminant analysis approach to MAR prediction
International Union of Pure and Applied Chemists
linear discriminant analysis
matrix attachment region
a cumulative probability MAR prediction tool
a MAR prediction tool to detect the MRS
the bipartite MAR recognition signature
a commercial implementation of marfinder
major histocompatibility complex
messenger ribonucleic acid protein
position weight matrices
stress induced duplex destabilization
scaffold/matrix attachment regions (synonymous with MAR)
a MAR prediction tool developed commercially by Genomatix
number of helical turns in a constrained DNA loop
wumber of superhelical turns in a constrained loop
Boulikas, T. Nature of DNA sequences at the attachment regions of genes to the nuclear matrix. J. Cell. Biochem. 52 (1993) 14–22.
Fawcett, D.W. On the occurrence of a fibrous lamina on the inner aspect of the nuclear envelope in certain cells of vertebrates. Am. J. Anat. 119 (1966) 129–145.
He, D., Zeng, C. and Brinkley, B.R. Nuclear matrix proteins as structural and functional components of the mitotic apparatus. Int. Rev. Cytol. 162B (1995) 1–74.
Stadler, S., Schnapp, V., Mayer, R., Stein, S., Cremer, C., Bonifer, C., Cremer, T and Dietzel, S. The architecture of chicken chromosome territories changes during differentiation. BMC Cell Biol. 5 (2004) 44.
Cremer, T. and Cremer, C. Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat. Rev. Genet. 2 (2001) 292–301.
Gotzmann, J. and Foisner, R. Lamins and lamin-binding proteins in functional chromatin organization. Crit. Rev. Eukaryot. Gene Expr. 9 (1999) 257–265.
Mika, S. NMP-db Available from: http://cubic.bioc.columbia.edu/db/nmpdb/.
Capco, D.G., Wan, K.M and Penman, S. The nuclear matrix: three-dimensional architecture and protein composition. Cell 29 (1982) 847–858.
Renz, A. and Fackelmayer, F.O. Purification and molecular cloning of the scaffold attachment factor B (SAF-B), a novel human nuclear protein that specifically binds to S/MAR-DNA. Nucleic Acids Res. 24 (1996) 843–849.
Kas, E. and Laemmli, U.K. In vivo topoisomerase II cleavage of the Drosophila histone and satellite III repeats: DNA sequence and structural characteristics. Embo. J. 11 (1992) 705–716.
Dickinson, L.A., Joh, T., Kohwi, Y. and Kohwi-Shigematsu, T. A tissue-specific MAR/SAR DNA-binding protein with unusual binding site recognition. Cell 70 (1992) 631–645.
Zong, R.T. and Scheuermann, R.H. Mutually exclusive interaction of a novel matrix attachment region binding protein and the NF-muNR enhancer repressor. Implications for regulation of immunoglobulin heavy chain expression. J. Biol. Chem. 270 (1995) 24010–24018.
Yusufzai, T.M. and Felsenfeld, G. The 5′-HS4 chicken beta-globin insulator is a CTCF-dependent nuclear matrix-associated element. Proc. Natl. Acad. Sci. U. S. A. 101 (2004) 8620–8624.
Steinert, P.M. and Roop, D.R. Molecular and cellular biology of intermediate filaments. Annu. Rev. Biochem. 57 (1988) 593–625.
Rando, O.J., Zhao, K and Crabtree, G.R. Searching for a function for nuclear actin. Trends Cell Biol. 10 (2000) 92–97.
He, D.C., Nickerson, J.A and Penman, S. Core filaments of the nuclear matrix. J. Cell Biol. 110 (1990) 569–580.
Narayan, K.S., Steele, W.J., Smetana, K and Busch, H. Ultrastructural aspects of the ribonucleo-protein network in nuclei of Walker tumor and rat liver. Exp. Cell Res. 46 (1967) 65–77.
Ma, H., Siegel, A.J and Berezney, R. Association of chromosome territories with the nuclear matrix. Disruption of human chromosome territories correlates with the release of a subset of nuclear matrix proteins. J. Cell Biol. 146 (1999) 531–542.
Miralles, F., Ofverstedt, L.G., Sabri, N., Aissouni, Y., Hellman, U., Skoglund, U and Visa, N. Electron tomography reveals posttranscriptional binding of pre-mRNPs to specific fibers in the nucleoplasm. J. Cell Biol. 148 (2000) 271–282.
Jackson, D.A. and Cook, P.R. Visualization of a filamentous nucleoskeleton with a 23 nm axial repeat. EMBO. J. 7 (1988) 3667–3677.
Earnshaw, W.C. and Heck, M.M. Localization of topoisomerase II in mitotic chromosomes. J. Cell Biol. 100 (1985) 1716–1725.
Glazkov, M.V., Poltaraus, A.B. and Lebedeva, I.A. Nucleotide sequence of DNA isolated from protein cores of rosette-like structures (elementary chromomeres) of mouse interphase chromosomes. Genetika 30 (1994) 1146–1154.
Prusov, A.N., Poliakov, V., Zatsepina, O.V., Fais, D. and Chentsov Iu, S. Isolation of rosette-like structures from partially deproteinized chromatin in rat hepatocytes. Tsitologiia 27 (1985) 1026–1030.
van Driel, R. and Fransz, P. Nuclear architecture and genome functioning in plants and animals: what can we learn from both? Exp. Cell Res. 296 (2004) 86–90.
Ierardi, L.A., Moss, S.B. and Bellve, A.R. Synaptonemal complexes are integral components of the isolated mouse spermatocyte nuclear matrix. J. Cell Biol. 96 (1983) 1717–1726.
Gautier, T., Robert-Nicoud, M., Guilly, M.N. and Hernandez-Verdun, D. Relocation of nucleolar proteins around chromosomes at mitosis. A study by confocal laser scanning microscopy. J. Cell Sci. 102 (Pt 4) (1992) 729–737.
Hernandez-Verdun, D. and Gautier, T. The chromosome periphery during mitosis. Bioessays 16 (1994) 179–185.
Berezney, R., Mortillaro, M.J., Ma, H., Wei, X. and Samarabandu, J. The nuclear matrix: a structural milieu for genomic function. Int. Rev. Cytol. 162A (1995) 1–65.
Abney, J.R., Cutler, B., Fillbach, M.L., Axelrod, D. and Scalettar, B.A. Chromatin dynamics in interphase nuclei and its implications for nuclear structure. J. Cell Biol. 137 (1997) 1459–1468.
Vogelstein, B., Pardoll, D.M. and Coffey, D.S. Supercoiled loops and eucaryotic DNA replicaton. Cell 22 (1980) 79–85.
Ostermeier, G.C., Liu, Z., Martins, R.P., Bharadwaj, R.R., Ellis, J., Draghici, S. and Krawetz, S.A. Nuclear matrix association of the human beta-globin locus utilizing a novel approach to quantitative real-time PCR. Nucleic Acids Res. 31 (2003) 3257–3266.
Mielke, C., Kohwi, Y., Kohwi-Shigematsu, T. and Bode, J. Hierarchical binding of DNA fragments derived from scaffold-attached regions: correlation of properties in vitro and function in vivo. Biochemistry 29 (1990) 7475–7485.
Kramer, J.A., Adams, M.D., Singh, G.B., Doggett, N.A. and Krawetz, S.A. Extended analysis of the region encompassing the PRM1→PRM2→TNP2 domain: genomic organization, evolution and gene identification. J. Exp. Zool. 282 (1998) 245–253.
Laborador, M. and Corces, V.G. Setting the boundaries of chromatin domains and nuclear organization. Cell 111 (2002) 151–154.
Williams, R.R. Transcription and the territory: the ins and outs of gene positioning. Trends Genet. 19 (2003) 298–302.
Heun, P., Laroche, T., Shimada, K., Furrer, P and Gasser, S.M. Chromosome dynamics in the yeast interphase nucleus. Science 294 (2001) 2181–2186.
Melcak, I., Cermanova, S., Jirsova, K., Koberna, K., Malinsky, J. and Raska, I. Nuclear pre-mRNA compartmentalization: trafficking of released transcripts to splicing factor reservoirs. Mol. Biol. Cell 11 (2000) 497–510.
Donev, R.M., Doneva, T.A., Bowen, W.R. and Sheer, D. HnRNP-A1 binds directly to double-stranded DNA in vitro within a 36 bp sequence. Mol. Cell. Biochem. 233 (2002) 181–185.
Cremer, T., Kupper, K., Dietzel, S and Fakan, S. Higher order chromatin architecture in the cell nucleus: on the way from structure to function. Biol. Cell 96 (2004) 555–567.
Krawetz, S.A., Draghici, S., Goodrich, R., Liu, Z and Ostermeier, G.C., In Silico and wet-bench identification of nuclear matrix attachment regions. in: Hypertension, Methods and Protocols (Fennell, J.P., Baker, A.H., Eds.), Vol. 108, Humana Press, 2004, 439–458.
Bode, J., Stengert-Iber, M., Kay, V., Schlake, T and Dietz-Pfeilstetter, A. Scaffold/matrix-attached regions: topological switches with multiple regulatory functions. Crit. Rev. Eukaryot. Gene Expr. 6 (1996) 115–138.
Kramer, J.A., McCarrey, J.R., Djakiew, D and Krawetz, S.A. Differentiation: the selective potentiation of chromatin domains. Development 125 (1998) 4749–4755.
Gerasimova, T.I. and Corces, V.G. Boundary and insulator elements in chromosomes. Curr. Opin. Genet. Dev. 6 (1996) 185–192.
Cook, P.R. The organization of replication and transcription. Science 284 (1999) 1790–1795.
Leonhardt, H., Rahn, H.P., Weinzierl, P., Sporbert, A., Cremer, T., Zink, D and Cardoso, M.C. Dynamics of DNA replication factories in living cells. J. Cell Biol. 149 (2000) 271–280.
Strissel, P.L., Espinosa, R., III, Rowley, J.D and Swift, H. Scaffold attachment regions in centromere-associated DNA. Chromosoma 105 (1996) 122–133.
Lammerding, J., Schulze, P.C., Takahashi, T., Kozlov, S., Sullivan, T., Kamm, R.D., Stewart, C.L and Lee, R.T. Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction. J. Clin. Invest. 113 (2004) 370–378.
Vorlickova, M., Chladkova, J., Kejnovska, I., Fialova, M and Kypr, J. Guanine tetraplex topology of human telomere DNA is governed by the number of (TTAGGG) repeats. Nucleic Acids Res. 33 (2005) 5851–5860.
Moyzis, R.K., Buckingham, J.M., Cram, L.S., Dani, M., Deaven, L.L., Jones, M.D., Meyne, J., Ratliff, R.L and Wu, J.R. A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc. Natl. Acad. Sci. U.S.A. 85 (1988) 6622–6626.
Lobov, I.B., Tsutsui, K., Mitchell, A.R and Podgornaya, O.I. Specificity of SAF-A and lamin B binding in vitro correlates with the satellite DNA bending state. J. Cell. Biochem. 83 (2001) 218–229.
Frisch, M., Frech, K., Klingenhoff, A., Cartharius, K., Liebich, I and Werner, T. In silico prediction of scaffold/matrix attachment regions in large genomic sequences. Genome Res. 12 (2002) 349–354.
Singh, G.B., Kramer, J.A and Krawetz, S.A. Mathematical model to predict regions of chromatin attachment to the nuclear matrix. Nucleic Acids Res. 25 (1997) 1419–1425.
van Drunen, C.M., Sewalt, R.G., Oosterling, R.W., Weisbeek, P.J., Smeekens, S.C and van Driel, R. A bipartite sequence element associated with matrix/scaffold attachment regions. Nucleic Acids Res. 27 (1999) 2924–2930.
Rudd, S., Frisch, M., Grote, K., Meyers, B.C., Mayer, K and 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. 135 (2004) 715–722.
Morgenstern, B., Dress, A and Werner, T. Multiple DNA and protein sequence alignment based on segment-to-segment comparison. Proc. Natl. Acad. Sci. U.S.A. 93 (1996) 12098–12103.
Needleman, S.B. and Wunsch, C.D. A general method applicable to the search for similarities in the amino acid sequence of two proteins. J. Mol. Biol. 48 (1970) 443–453.
Quandt, K., Frech, K., Karas, H., Wingender, E and Werner, T. MatInd and MatInspector: new fast and versatile tools for detection of consensus matches in nucleotide sequence data. Nucleic Acids Res. 23 (1995) 4878–4884.
Wolfertstetter, F., Frech, K., Herrmann, G and Werner, T. Identification of functional elements in unaligned nucleic acid sequences by a novel tuple search algorithm. Comput. Appl. Biosci. 12 (1996) 71–80.
Tarhio, J. and Ukkonen, E. Approximate Boyer-Moore String Matching. 2005; Available from: http://www.cs.hut.fi/:_tarhio/papers/abm.ps.gz.
RA Baeza-Yates, G.G. Fast text searching for regular expressions or automaton searching on tries. Journal of the A.C.M. 43 (1996) 915–936.
Donev, R., Horton, R., Beck, S., Doneva, T., Vatcheva, R., Bowen, W.R and Sheer, D. Recruitment of heterogeneous nuclear ribonucleoprotein A1 in vivo to the LMP/TAP region of the major histocompatibility complex. J. Biol. Chem. 278 (2003) 5214–5226.
Wang, H., Noordewier, M and Benham, C.J. Stress-induced DNA duplex destabilization (SIDD) in the E. coli genome: SIDD sites are closely associated with promoters. Genome Res. 14 (2004) 1575–1584.
Bi, C. and Benham, C.J. WebSIDD: server for predicting stress-induced duplex destabilized (SIDD) sites in superhelical DNA. Bioinformatics 20 (2004) 1477–1479.
Benham, C.J. and Bi, C. The analysis of stress-induced duplex destabilization in long genomic DNA sequences. J. Comput. Biol. 11 (2004) 519–543.
Benham, C., Kohwi-Shigematsu, T and Bode, J. Stress-induced duplex DNA destabilization in scaffold/matrix attachment regions. J. Mol. Biol. 274 (1997) 181–196.
Bode, J., Kohwi, Y., Dickinson, L., Joh, T., Klehr, D., Mielke, C and Kohwi-Shigematsu, T. Biological significance of unwinding capability of nuclear matrix-associating DNAs. Science 255 (1992) 195–197.
Vassetzky, Y.S., Bogdanova, A.N and Razin, S.V. Analysis of the chicken DNA fragments that contain structural sites of attachment to the nuclear matrix: DNA-matrix interactions and replication. J. Cell. Biochem. 79 (2000) 1–14.
Girard-Reydet, C., Gregoire, D., Vassetzky, Y and Mechali, M. DNA replication initiates at domains overlapping with nuclear matrix attachment regions in the xenopus and mouse c-myc promoter. Gene 332 (2004) 129–138.
Beaudouin, J., Gerlich, D., Daigle, N., Eils, R and Ellenberg, J. Nuclear envelope breakdown proceeds by microtubule-induced tearing of the lamina. Cell 108 (2002) 83–96.
Benham, C.J. Stress-induced DNA duplex destabilization in transcriptional initiation. Pac. Symp. Biocomput. (2001) 103–114.
Benham, C.J. Torsional stress and local denaturation in supercoiled DNA. Proc. Natl. Acad. Sci. U.S.A. 76 (1979) 3870–3874.
Fye, R.M. and Benham, C.J. Exact method for numerically analyzing a model of local denaturation in superhelically stressed DNA. Phys. Rev. E. 59 (1999) 3408–3426.
Chengpeng Bi, C.J.B. The approximate algorithm for analysis of the strand separation transition in super helical DNA using nearest neighbor energetics. Proceedings of the IEEE Computer Society Conference on Bioinformatics (2003) 460.
Rogozin, I.B., Glazko, G.V and Glazkov, M.V. Computer prediction of sites associated with various elements of the nuclear matrix. Brief. Bioinform. 1 (2000) 33–44.
Glazko, G.V., Rogozin, I.B and Glazkov, M.V. Comparative study and prediction of DNA fragments associated with various elements of the nuclear matrix. Biochim. Biophys. Acta 1517 (2001) 351–364.
Baldi, P. and Brunak, S. Bioinformatics: the machine learning approach: Adaptive computation and machine learning. (Dietterich, T., Ed.), 2nd edition, MIT Press, Cambridge, Mass., 2001, 1–452.
Kramer, J.A., Adams, M.D., Singh, G.B., Doggett, N.A and Krawetz, S.A. A matrix associated region localizes the human SOCS-1 gene to chromosome 16p13.13. Somat. Cell Mol. Genet. 24 (1998) 131–133.
Singh, G.B. and Krawetz, S.A., Data Mining for Discovering Matrix Association Regions (MARs). in: Data mining and knowledge discovery: theory, toolsand technology II. (Dasarathy, B.V.E., Ed.), Proceedings of Spie, (2000) 330–341.
Purbowasito, W., Suda, C., Yokomine, T., Zubair, M., Sado, T., Tsutsui, K and Sasaki, H. Large-scale identification and mapping of nuclear matrix-attachment regions in the distal imprinted domain of mouse chromosome 7. DNA Res. 11 (2004) 391–407.
Ubbink, J. and Odijk, T. Electrostatic-undulatory theory of plectonemically supercoiled DNA. Biophys. J. 76 (1999) 2502–2519.
Belmont, A.S., Sedat, J.W and Agard, D.A. A three-dimensional approach to mitotic chromosome structure: evidence for a complex hierarchical organization. J. Cell Biol. 105 (1987) 77–92.
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