Matrix attachment regions and transcription units in a polygenic mammalian locus overlapping two isochores

Fernandez, M. A.; Baron, Bruno; Prigent, Magali; Toledo, Franck; Buttin, Gérard; Debatisse, Michèlle

doi:10.1002/(sici)1097-4644(19971215)67:4<541::aid-jcb11>3.0.co;2-c

Cited by 21 publications

(22 citation statements)

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“…Interestingly, the LAR region studied here was previously found to contain a cluster of MAR elements [Fernandez et al, 1997]. In the latter work, three other regions containing MAR elements were found, but none of them was identified as a LAR in the present study.…”

Section: Resultssupporting

confidence: 52%

Mammalian recombination hot spot in a DNA loop anchorage region: A model for the study of common fragile sites

2001

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We analyzed the replication pattern and the topological organization of a 200 kb long Chinese hamster polygenic locus, which spans the boundary of two isochores. One of them is G C rich while the second one is highly A T rich. Previous analysis of mutants ampli®ed for this locus had identi®ed, within the A T rich isochore, a mitotic recombination hotspot and a replication origin separated by some 7 kb. The recombination hotspot exhibits structural features repeatedly observed at common fragile sites, including a typical enrichment in peaks of enhanced DNA helix exibility. By studying the replication pattern of the same locus in the non-ampli®ed CHO cells, we con®rm here the localization of the replication origin and show that the mitotic recombination hotspot does not correspond to a replicon junction. This ®nding makes questionable current hypotheses correlating replication termination regions with recombination prone sequences. Using topoisomerase II-mediated DNA cleavage at matrix attachment sites, we identi®ed a 40 kb-long DNA anchorage region extending all along a transcription unit nested within the A T rich isochore. Both the recombination hotspot and the replication origin lie within this topoisomerase II sensitive region, which suggests that features essential for initiation of recombination and initiation of DNA replication cluster within DNA anchorage regions. Features common to this region and to common fragile sites are discussed.

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Section: Resultssupporting

confidence: 52%

Mammalian recombination hot spot in a DNA loop anchorage region: A model for the study of common fragile sites

2001

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“…Thus, we might be tempted to think of %AT as a good predictor of binding strength. However, high AT content alone is not sufficient for MAR function (44,47,60,61). Although %AT per se may not be useful, we propose that the following refinement may be useful.…”

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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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“…Были исследованы последовательности из GenBank, отнесенные к группе MARs/SARs: фрагменты ДНК золотистого хомяка C. aureus, связывающиеся с ядерным матриксом (Х96546 -Х96549 [15]), фрагменты ДНК клеток табака (AF065877-AF065888) [16], фрагменты 19-ой хромосомы человека (Z35288, Z35290, Z35291, Z35279, Z35280, Z35282) [17], фрагменты хромосомы человеческого бета-глобинового комплекса [18], область между генами гистонами H1 и H3 плодовой мухи D. melanogaster [6], MARs последовательности для региона гена бета-интерферона человека [19], MARs последовательности, отстоящие от 5'-конца гена лизоцима Gallus Gallus [20] на 11.1 т.п.н. Для приведенных последовательностей построены карты зависимости потенциала нуклеосомного позиционирования вдоль длины фрагмента.…”

Section: результаты исследованияunclassified

Multiple Sites of the Nucleosome-Positioning Are Associated with the Matrix Associated Regions (MARs/SARs)

Fedoseeva¹,

Fedoseyeva²

2007

Math.Biol.Bioinf.

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Matrix attachment regions and transcription units in a polygenic mammalian locus overlapping two isochores

Cited by 21 publications

References 47 publications

Mammalian recombination hot spot in a DNA loop anchorage region: A model for the study of common fragile sites

Mammalian recombination hot spot in a DNA loop anchorage region: A model for the study of common fragile sites

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

Multiple Sites of the Nucleosome-Positioning Are Associated with the Matrix Associated Regions (MARs/SARs)

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Matrix attachment regions and transcription units in a polygenic mammalian locus overlapping two isochores

Cited by 21 publications

References 47 publications

Mammalian recombination hot spot in a DNA loop anchorage region: A model for the study of common fragile sites

Mammalian recombination hot spot in a DNA loop anchorage region: A model for the study of common fragile sites

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

Multiple Sites of the Nucleosome-Positioning Are Associated with the Matrix Associated Regions (MARs/SARs)

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