In-silico prediction and observations of nuclear matrix attachment

Abstract

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.

Genomewide identification of nuclear matrix attachment regions: an analysis of methods

“…MARs are often characterized as AT-rich regions or those containing topoisomerase II or other binding sites [31]. These two characteristics alone are not sufficient for nuclear matrix binding [32,33].…”

Reconfiguration of genomic anchors upon transcriptional activation of the human major histocompatibility complex

“…These sequences have been called scaffold attachment regions (SARs) in metaphase cells (Paulson and Laemmli 1977). MARs are associated with sequence motifs rich in AT tracts, repetitive sequences, topoisomerase binding sites, and regions of DNA with a propensity for base unpairing (Liebich et al 2002;Platts et al 2006;Ottaviani et al 2008). The Multi-Loop Subcompartment model of chromatin folding predicts rosettes containing loops of 120 kb (Münkel et al 1999).…”

“…Due to the limited scale of these methods only a few hundred of these sequences have been experimentally identified. Although computational methods have been developed to determine their positions on a larger scale, progress has been hampered by the limited number of MARs that have been experimentally defined as well as the fact that some MARs may not be permanently attached to the nuclear matrix (Platts et al 2006;Girod et al 2007;Linnemann et al 2007). Microarray technology now provides an opportunity to map MARs at high resolution across the genome and address their role in gene expression.…”

Revisiting the function of nuclear scaffold/matrix binding proteins in X chromosome inactivation

“…13 Although individual S/MARs were originally identified using experimental approaches, several studies have predicted the sites of the S/MARs using computational analyses. 14 Interestingly, the computationally identified S/MARs distribute in a high density on the X chromosome compared with the other autosomes. 15 More strikingly, the LINE sequences are overrepresented by nearly two-fold among the human S/MARs, relative to their overall abundance in the human or mouse genome.…”