Correlations between scaffold/matrix attachment region (S/MAR) binding activity and DNA duplex destabilization energy.
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.
Bode
Jürgen
J
German Research Center for Biotechnology, RDIF/Epigenetic Regulation, D-38124 Braunschweig, Mascheroder Weg 1, Germany. jbo@gbf.de
Winkelmann
Silke
S
Götze
Sandra
S
Spiker
Steven
S
Tsutsui
Ken
K
Bi
Chengpeng
C
A K
Prashanth
P
Benham
Craig
C
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism; D002843:Chromatin / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D019281:Dimerization; D015894:Genome, Human; D018745:Genome, Plant; D006801:Humans; D016899:Interferon-beta / Q000737:chemistry / Q000378:metabolism; D045170:Matrix Attachment Regions; D009690:Nucleic Acid Conformation; D009692:Nucleic Acid Heteroduplexes / Q000378:metabolism*; D011485:Protein Binding
D000970:Antineoplastic Agents; D002843:Chromatin; D009692:Nucleic Acid Heteroduplexes; D016899:Interferon-beta; D004247:DNA