The term S/MAR (scaffold/matrix attachment region), otherwise called SAR (scaffold-attachment region), or MAR (matrix-associated region), are sequences in the DNA of

eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

chromosomes where the

nuclear matrix In biology, the nuclear matrix is the network of fibres found throughout the inside of a cell nucleus after a specific method of chemical extraction. According to some it is somewhat analogous to the cell cytoskeleton. In contrast to the cytoskelet ...

attaches. As architectural DNA components that organize the

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

of eukaryotes into functional units within the

cell nucleus The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, h ...

, S/MARs mediate structural organization of the

chromatin Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...

within the nucleus. These elements constitute anchor points of the DNA for the chromatin scaffold and serve to organize the chromatin into structural domains. Studies on individual genes led to the conclusion that the dynamic and complex organization of the chromatin mediated by S/MAR elements plays an important role in the regulation of

gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...

Overview

It has been known for many years that a polymer meshwork, a so-called "

" or "nuclear-scaffold" is an essential component of eukaryotic nuclei. This nuclear skeleton acts as a dynamic support for many specialized events concerning the readout a spread of genetic information (see below). S/MARs map to non-random locations in the genome. They occur at the flanks of transcribed regions, in 5´-

intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of the cistron .e., gene. ...

s, and also at gene breakpoint cluster regions (BCRs). Being association points for common nuclear structural proteins S/MARs are required for authentic and efficient chromosomal replication and

transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...

, for recombination and chromosome condensation. S/MARs do not have an obvious consensus sequence. Although prototype elements consist of AT-rich regions several hundred base pairs in length, the overall base composition is definitely not the primary determinant of their activity. Instead, their function requires a pattern of "AT-patches" that confer the propensity for local strand unpairing under torsional strain.

Bioinformatics Bioinformatics () is an interdisciplinary field that develops methods and software tools for understanding biological data, in particular when the data sets are large and complex. As an interdisciplinary field of science, bioinformatics combi ...

approaches support the idea that, by these properties, S/MARs not only separate a given transcriptional unit (chromatin domain) from its neighbors, but also provide platforms for the assembly of factors enabling transcriptional events within a given domain. An increased propensity to separate the DNA strands (the so-called 'stress induced duplex destabilization' potential, SIDD) can serve the formation of secondary structures such as cruciforms or slippage structures, which are recognizable features for a number of

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

s (

DNAse Deoxyribonuclease (DNase, for short) refers to a group of glycoprotein endonucleases which are enzymes that catalyze the hydrolytic cleavage of phosphodiester linkages in the DNA backbone, thus degrading DNA. The role of the DNase enzyme in cells ...

topoisomerase DNA topoisomerases (or topoisomerases) are enzymes that catalyze changes in the topological state of DNA, interconverting relaxed and supercoiled forms, linked (catenated) and unlinked species, and knotted and unknotted DNA. Topological issues i ...

poly(ADP-ribosyl) polymerase Poly, from the Greek πολύς meaning "many" or "much", may refer to: Businesses * China Poly Group Corporation, a Chinese business group, and its subsidiaries: ** Poly Property, a Hong Kong incorporated Chinese property developer ** Poly Real ...

s and enzymes of the histone-acetylation and DNA-methylation apparatus). S/MARs have been classified as either being constitutive (acting as permanent domain boundaries in all cell types) or facultative (cell type- and activity-related) depending on their dynamic properties. While the number of S/MARs in the

human genome The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the n ...

has been estimated to approach 64,000 (chromatin domains) plus an additional 10,000 (replication foci), in 2007 still only a minor fraction (559 for all eukaryotes) had met the standard criteria for an annotation in the S/MARt database.

Context-dependent properties

Current views of the

envision it as a dynamic entity, which changes its properties along the requirements of the cell nucleus—much the same as the

cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...

adapts its structure and function to external signals. In retrospect it is of note that the discovery of S/MARs has two major routes: * the description of scaffold-attachment elements (SARs) by Laemmli and coworkers, which were thought to demarcate the borders of a given chromatin domain * the characterization of matrix-associated regions (MARs) the first examples of which supported the immunoglobulin kapp-chain enhancer according to its occupancy with transcription factors Subsequent work demonstrated both the constitutive (SAR-like) and the facultative (MAR-like) function of the elements depending on the context. Whereas constitutive S/MARs were found to be associated with a

DNase I hypersensitive site In genetics, DNase I hypersensitive sites (DHSs) are regions of chromatin that are sensitive to cleavage by the DNase I enzyme. In these specific regions of the genome, chromatin has lost its condensed structure, exposing the DNA and making it acc ...

in 'all' cell types (whether or not the enclosed domain was transcribed), DNAse I hypersensitivity of the facultative type depended on the transcriptional status. The major difference between these two functional types of S/MARs is their size: the constitutive elements may extend over several kilobasepairs whereas facultative ones are at the lower size limit around 300 base pairs. The figure shows our present understanding of these properties and it incorporates the following findings: * the dynamic properties of S/MAR-scaffold contacts as derived by haloFISH investigations * the fact that during transcription DNA is reeled through RNA-polymerase which itself is a fixed component of the nuclear matrix * the fact that certain domain-intrinsic S/MARs require the support of an adjacent transcription factor to become active.

Use in gene therapy

As an alternative to viral vectors, which can have unwanted effects in patients body, non-viral methods of gene therapy are being studied. One of such methods uses

plasmids A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...

with special properties - the so-called episomes. Episomes have the ability to divide together with the rest of eukaryotic genome during mitosis. Compared with standard plasmids they are not epigenetically silenced within nucleus and are not enzymatically destroyed. Episomes acquire this ability through the presence of S/MAR sequence within their construct.

Additional information

Recently, Tetko has found a strong correlation of intragenic S/MARs with spatiotemporal expression of genes in ''

Arabidopsis thaliana ''Arabidopsis thaliana'', the thale cress, mouse-ear cress or arabidopsis, is a small flowering plant native to Eurasia and Africa. ''A. thaliana'' is considered a weed; it is found along the shoulders of roads and in disturbed land. A winter a ...

''. On a genome scale, pronounced tissue- and organ-specific and developmental expression patterns of S/MAR-containing genes have been detected. Notably,

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

genes contain a significant higher portion of S/MARs. The pronounced difference in expression characteristics of S/MAR-containing genes emphasizes their functional importance and the importance of structural chromosomal characteristics for gene regulation in plants as well as within other eukaryotes.

References

{{DEFAULTSORT:Scaffold matrix attachment region Molecular genetics