Stress-induced duplex DNA destabilization in scaffold/matrix attachment regions

Benham, Craig J.; Kohwi‐Shigematsu, Terumi; Bode, Jürgen

doi:10.1006/jmbi.1997.1385

Cited by 134 publications

(138 citation statements)

References 74 publications

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“…Sperry et al (1989) have ®rst shown that SARs are found at recombination sites of mammal genes. Consistent with this, Benham et al (1997) have shown, based on computational analysis, that SARs characteristically have DNA-destabilizing unwinding elements. SARs have high af®nity for the Topo II enzyme that has various functions to control the higher-order structure of genomic DNA such as relaxation of the supercoil DNA (Bode et al, 1995;Sperry et al, 1989).…”

Section: Discussionsupporting

confidence: 57%

“…Topoisomerase II (Topo II) recognition sites, unwinding elements and A-and T-tracts are known to be cis elements characteristic of SARs. Computational analysis (Benham et al, 1997;Bode et al, 2000) indicated that SARs have base-unpairing elements which destabilize DNA duplex in response to stress. Topo II introduces double-stranded breaks of DNA (Sperry et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

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Presence of an SAR‐like sequence in junction regions between an introduced transgene and genomic DNA of cultured tobacco cells: its effect on transformation frequency

et al. 2001

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SummaryA 12.5-kb DNA fragment with junction regions between the transgene and genomic DNA was cloned from a transgenic tobacco cell line obtained by microprojectile bombardment of plasmid pCaMVNEO. Nucleotide sequence analysis of the fragment (DDBJ accession no. D84238 ) showed that it carried a 7.7-kb core sequence (concatemer of a complete pCaMVNEO and a partial pCaMVNEO) and two identical 1.3-kb junction sequences that¯anked both the 5¢ and 3¢ ends of the core sequence and had inverted orientations. These sequences had topoisomerase II (Topo II) cleavage sites and adenine and thimine-rich sequences known to be speci®c to nuclear scaffold-attachment regions (SARs). An in vitro binding assay showed that a 507-bp fragment (designated TJ1 ) from the 1.3-kb sequence had the ability to bind to nuclear scaffold preparations of cultured tobacco cells, con®rmation that the 1.3-kb sequence is an SAR. Insertion of TJ1 at the 5¢ and 3¢ sides of the expression cassette for the npt II gene increased transformant yields 5-to 10-fold and the NPT II enzyme activity per copy of the gene 5-fold. TJ1 enhances the integration or expression of the transgene, or both. Clearly, TJ1 is very useful for producing transgenic plants. This is the ®rst report on an SAR-like sequence that is located in the transgene locus and enhances transformation ef®ciency in eukaryotic cells. The possible role of TJ1-SAR in the molecular evolution of plant genome is discussed.

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Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Presence of an SAR‐like sequence in junction regions between an introduced transgene and genomic DNA of cultured tobacco cells: its effect on transformation frequency

et al. 2001

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“…We have identified A-box and T-box motifs (54), the yeast ARS consensus sequence (55), the consensus sequence for Drosophila topoisomerase II (7,73), the base unpairing region (BUR) (4,5,63,64), the MAR recognition sequence (MRS) (44), origin of replication and homeotic protein recognition motifs (ORI), TG-rich sequences, curved DNA motifs, and kinked DNA motifs (56,57,65,66,68). The frequency of occurrence of these motifs in each MAR is listed in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…The base unpairing sequence (BUR) proposed by these workers to be diagnostic of MAR sequences was not highly correlated with binding strength in our tobacco MARs (r ) 0.55). However, this group has recently developed a more sophisticated computational analysis which emphasizes the presence and arrangement of stress-induced base unpairing regions (64). In the sequences they have analyzed to date, there is good correspondence between the parameters measured and sequences with MAR activity measured by in vitro binding assays.…”

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confidence: 99%

Characterization of Randomly-Obtained Matrix Attachment Regions (MARs) from Higher Plants^,

et al. 1999

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Matrix attachment regions (MARs) can be operationally defined as DNA fragments that bind to the nuclear matrix. We have created a library of randomly obtained MARs from tobacco (Nicotiana tobacum) by cloning DNA fragments that co-isolate with nuclear matrixes prepared by a method involving lithium diiodosalicylate. The interactions of several of the cloned MARs with nuclear matrixes were tested by an in vitro binding assay in which genomic DNA was used as competitor. Based on this assay, the MARs were classified as strong, medium, and weak binders. Examples of each of the binding classes were further studied by in vitro binding using self-and cross-competition. Estimates of dissociation constants for several MARs ranged from 6 to 11 nM and correlated inversely with binding strength. The number of binding sites per matrix for several MARs ranged from 4 × 10 5 to 9 × 10 5 and correlated directly with binding strength. We conclude that binding strength, as we have measured it, is a function of both numbers of binding sites and affinity for the sites. The tobacco MARs were sequenced and analyzed for overall AT content, for distribution of AT-rich regions, and for the abundance of several MAR-related motifs. Previously identified MAR motifs correlate to various degrees with binding strength. Notably, the Drosophila topoisomerase II motif does not correlate with binding strength of the tobacco MARs. A newly identified motif, the "90%AT Box," correlates better with binding strength than any of the previously identified motifs we investigated.The idea that chromatin is organized into loop domains is as old as the original observation of loops in lampbrush chromosomes by Flemming in 1882 (1, 2). A reincarnation of that idea came from the electron micrographs of Paulson and Laemmli (3), which showed loops of DNA attached at their bases to the proteinaceous scaffold of metaphase chromosomes. A natural extension of the observations of Paulson and Laemmli is that the DNA-chromosome scaffold interaction is not random. Indeed, abundant evidence has been presented for interactions between specific DNA fragments and the metaphase chromosome scaffold and the interphase nuclear matrix [reviewed in Bode et al. (4,5)]. The specific DNA sequences have been termed MARs (matrix associated regions) (6) or SARs (scaffold attachment regions) (7,8). Both terms apparently describe the same biological entity (9). We use the term "MAR" because of its prevalence in the literature (10).MARs have a typical size of around 1 kb and have been postulated to form the anchorage points of torsionally constrained loop domains ranging in size from a few kb to more than 100 kb [reviewed by Gasser et al. (11) and Bode et al. (4,5)]. These putative structural elements of chromatin have attracted considerable attention because of evidence for their involvement in the regulation of transcription, including stabilization and increased levels of transgene expression (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27) [reviewed by Bode e...

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“…Stress Induced DNA Duplex Destabilization (SIDD) analysis predicts the probability of double strand breakage under superhelical strain (Benham, 1996;1997;Bi and Benham, 2004). The algorithm calculates the energy required for each base pair to separate in a given sequence context.…”

Section: Sidd Analysismentioning

confidence: 99%

Neoplastic MiR‐17∼92 deregulation at a dna fragility motif (SIDD)

Schneider¹,

Nagel²,

Ehrentraut³

et al. 2011

Genes Chromosomes & Cancer

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Chromosomal or mutational activation of BCL6 (at 3q27) typifies diffuse large B‐cell lymphoma (DLBCL) which in the germinal center subtype may be accompanied by focal amplification of chromosome band 13q31 effecting upregulation of miR‐17∼92. Using long distance inverse‐polymerase chain reaction, we mapped and sequenced six breakpoints of a complex BCL6 rearrangement t(3;13)(q27;q31)t(12;13)(p11;q31) in DLBCL cells, which places miR‐17∼92 antisense within the resulting ITPR2‐BCL6 chimeric fusion gene rearrangement. MiR‐17∼92 members were upregulated ∼15‐fold over controls in a copy number independent manner consistent with structural deregulation. MIR17HG and ITPR2‐BCL6 were, despite their close configuration, independently expressed, discounting antisense regulation. MIR17HG in t(3;13)t(12;13) cells proved highly responsive to treatment with histone deacetylase inhibitors implicating epigenetic deregulation, consistent with which increased histone‐H3 acetylation was detected by chromatin immunoprecipitation near the upstream MIR17HG breakpoint. Remarkably, 5/6 DNA breaks in the t(3;13)t(12;13) precisely cut at stress‐induced DNA duplex destabilization (SIDD) peaks reminiscent of chromosomal fragile sites, while the sixth lay 150 bp distant. Extended SIDD profiling showed that additional oncomiRs also map to SIDD peaks. Fluorescence in situ hybridization analysis showed that 11 of 52 (21%) leukemia‐lymphoma (L‐L) cell lines with 13q31 involvement bore structural rearrangements at/near MIR17HG associated with upregulation. As well as fueling genome instability, SIDD peaks mark regulatory nuclear‐scaffold matrix attachment regions open to nucleosomal acetylation. Collectively, our data indict a specific DNA instability motif (SIDD) in chromosome rearrangement, specifically alterations activating miR‐17∼92 epigenetically via promoter hyperacetylation, and supply a model for the clustering of oncomiRs near cancer breakpoints. © 2011 Wiley Periodicals, Inc.

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Stress-induced duplex DNA destabilization in scaffold/matrix attachment regions

Cited by 134 publications

References 74 publications

Presence of an SAR‐like sequence in junction regions between an introduced transgene and genomic DNA of cultured tobacco cells: its effect on transformation frequency

Presence of an SAR‐like sequence in junction regions between an introduced transgene and genomic DNA of cultured tobacco cells: its effect on transformation frequency

Characterization of Randomly-Obtained Matrix Attachment Regions (MARs) from Higher Plants^,

Neoplastic MiR‐17∼92 deregulation at a dna fragility motif (SIDD)

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Stress-induced duplex DNA destabilization in scaffold/matrix attachment regions

Cited by 134 publications

References 74 publications

Presence of an SAR‐like sequence in junction regions between an introduced transgene and genomic DNA of cultured tobacco cells: its effect on transformation frequency

Presence of an SAR‐like sequence in junction regions between an introduced transgene and genomic DNA of cultured tobacco cells: its effect on transformation frequency

Characterization of Randomly-Obtained Matrix Attachment Regions (MARs) from Higher Plants,

Neoplastic MiR‐17∼92 deregulation at a dna fragility motif (SIDD)

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Characterization of Randomly-Obtained Matrix Attachment Regions (MARs) from Higher Plants^,