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Correlations between scaffold/matrix attachment region (S/MAR) binding activity and DNA duplex destabilization energy.

Abstract：

:Scaffold or matrix-attachment regions (S/MARs) are thought to be involved in the organization of eukaryotic chromosomes and in the regulation of several DNA functions. Their characteristics are conserved between plants and humans, and a variety of biological activities have been associated with them. The identification of S/MARs within genomic sequences has proved to be unexpectedly difficult, as they do not appear to have consensus sequences or sequence motifs associated with them. We have shown that S/MARs do share a characteristic structural property, they have a markedly high predicted propensity to undergo strand separation when placed under negative superhelical tension. This result agrees with experimental observations, that S/MARs contain base-unpairing regions (BURs). Here, we perform a quantitative evaluation of the association between the ease of stress-induced DNA duplex destabilization (SIDD) and S/MAR binding activity. We first use synthetic oligomers to investigate how the arrangement of localized unpairing elements within a base-unpairing region affects S/MAR binding. The organizational properties found in this way are applied to the investigation of correlations between specific measures of stress-induced duplex destabilization and the binding properties of naturally occurring S/MARs. For this purpose, we analyze S/MAR and non-S/MAR elements that have been derived from the human genome or from the tobacco genome. We find that S/MARs exhibit long regions of extensive destabilization. Moreover, quantitative measures of the SIDD attributes of these fragments calculated under uniform conditions are found to correlate very highly (r2>0.8) with their experimentally measured S/MAR-binding strengths. These results suggest that duplex destabilization may be involved in the mechanisms by which S/MARs function. They suggest also that SIDD properties may be incorporated into an improved computational strategy to search genomic DNA sequences for sites having the necessary attributes to function as S/MARs, and even to estimate their relative binding strengths.

journal_name

J Mol Biol

journal_title

Journal of molecular biology

authors

Bode J,Winkelmann S,Götze S,Spiker S,Tsutsui K,Bi C,A K P,Benham C

doi

10.1016/j.jmb.2005.11.073

keywords:

subject

Has Abstract

pub_date

2006-04-28 00:00:00

pages

597-613

issue

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(05)01509-3

journal_volume

358

pub_type

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Correlations between scaffold/matrix attachment region (S/MAR) binding activity and DNA duplex destabilization energy.