Differential nuclear scaffold/matrix attachment marks expressed genes†

Abstract

It is well established that nuclear architecture plays a key role in poising regions of the genome for transcription. This may be achieved using scaffold/matrix attachment regions (S/MARs) that establish loop domains. However, the relationship between changes in the physical structure of the genome as mediated by attachment to the nuclear scaffold/matrix and gene expression is not clearly understood. To define the role of S/MARs in organizing our genome and to resolve the often contradictory loci-specific studies, we have surveyed the S/MARs in HeLa S3 cells on human chromosomes 14–18 by array comparative genomic hybridization. Comparison of LIS (lithium 3,5-diiodosalicylate) extraction to identify SARs and 2 m NaCl extraction to identify MARs revealed that approximately one-half of the sites were in common. The results presented in this study suggest that SARs 5′ of a gene are associated with transcript presence whereas MARs contained within a gene are associated with silenced genes. The varied functions of the S/MARs as revealed by the different extraction methods highlights their unique functional contribution.

Functional Nuclear Organization of Transcription and DNA Replication: A Topographical Marriage between Chromatin Domains and the Interchromatin Compartment

“…Our data suggest that scaffold/matrix attachment regions (S/MARs), which establish loop domains and have a key role in priming regions of the genome for transcription (Linnemann et al 2009), are located in the PR. A nuclear matrix has been proposed as "the site of organization for replication, transcription and posttranscriptional processing" (Berezney and Coffey 1975;Berezney et al 1995).…”

Programming DNA replication origins and chromosome organization

“…Matrix attachment sites are also associated with binding sites for topoisomerase II (Razin et al 1991), an enzyme which is essential for loop remodeling. Recently, the first genome-wide studies to localize MARs were performed in human cells (Linnemann et al 2007;Linnemann et al 2009). As expected, a significant proportion of MARs were found to be associated with expressed genes.…”

DNA polymorphism and epigenetic marks modulate the affinity of a scaffold/matrix attachment region to the nuclear matrix

“…S/MARs anchor chromatin onto the NM, thereby organizing the genomic DNA into topologically distinct loop domains that are important for the regulation of replication and transcription. 2 Despite numerous genomic studies, [3][4][5][6][7] no consensus S/MAR sequence has been identified so far. 8 S/MARs can be both A/T 9 or G/C rich.…”