marscan

Function

Description

Matrix/scaffold attachment regions (MARs/SARs) are genomic elements thought to delineate the structural and functional organisation of the eukaryotic genome. Originally, MARs and SARs were identified through their ability to bind to the nuclear matrix or scaffold. Binding cannot be assigned to a unique sequence element, but is dispersed over a region of several hundred base pairs. These elements are found flanking a gene or a small cluster of genes and are located often in the vicinity of cis-regulatory sequences. This has led to the suggestion that they contribute to higher order regulation of transcription by defining boundaries of independently controlled chromatin domains. There is indirect evidence to support this notion. In transgenic experiments MARs/SARs dampen position effects by shielding the transgene from the effects of the chromatin structure at the site of integration. Furthermore, they may act as boundary elements for enhancers, restricting their long range effect to only the promoters that are located in the same chromatin domain.

marscan finds a bipartite sequence element that is unique for a large group of eukaryotic MARs/SARs. This MAR/SAR recognition signature (MRS) comprises two individual sequence elements that are <200 bp apart and may be aligned on positioned nucleosomes in MARs. The MRS can be used to correctly predict the position of MARs/SARs in plants and animals, based on genomic DNA sequence information alone. Experimental evidence from the analysis of >300 kb of sequence data from several eukaryotic organisms show that wherever a MRS is observed in the DNA sequence, the corresponding genomic fragment is a biochemically identifiable SAR.

The MRS is a bipartite sequence element that consists of two individual sequences of 8 (AATAAYAA) and 16 bp (AWWRTAANNWWGNNNC) within a 200 bp distance from each other. One mismatch is allowed in the 16 bp pattern. The patterns can occur on either strand of the DNA with respect to each other. The 8 bp and the 16 bp sites can overlap.

Where there are many possible MRS sites caused by many 8 bp and/or 16 bp pattern sites located within 200 bp of each other, then only the 8 bp site and the 16 bp site that occur closest to each other are reported.

Once a MRS has been reported, no more sites will be looked for within 200 bp of that site. This reduces (but maybe will not totally eliminate) over-reporting of the clusters of MRS's that tend to occur within a MAR/SAR.

Not all SARs contain a MRS. Analysis of >300 kb of genomic sequence from a variety of eukaryotic organisms shows that the MRS faithfully predicts 80% of MARs and SARs, suggesting that at least one other type of MAR/SAR may exist which does not contain a MRS.

It it still not at all clear whether MAR/SARs are real biological phenomena or just experimental artefacts.

The problem of how to define and find MARs is still being actively invetsigated. For a recent evaluation of this method and others, see reference 3.

Usage

Command line arguments


Input file format

marscan reads a normal genomic DNA USA.

Output file format

By default marscan writes a GFF (Gene Feature Format) report file.

Data files

None.

Notes

It does not check whether the DNA input sequence is genomic or not.

References

  1. The method for finding the MAR/SAR sites is described in:

    van Drunen CM., Sewalt RGAB., Oosterling RW., Weisbeek PJ., Smeekens SCM. and van Driel R. "A bipartite sequence element associated with matrix/scaffold attachment regions" Nucleic Acids Research. 1999. Vol 27, No. 14, pp. 2924-2930

  2. The original paper on MARs/SARs is:

    Mirkovitch J., Mirault M-E. and Laemmli UK. Cell. 1984. Vol. 39 pp. 223-232.

  3. A recent evaluation of methods to find MARs/SARs:

    I. Liebich, J. Bode, I. Reuter and E. Wingender "Evaluation of sequence motifs found in scaffold/matrix-attached regions (S/MARs)" Nucleic Acids Research 2002, Vol. 30, No. 15 3433-3442

Warnings

None

Diagnostic Error Messages

None.

Exit status

It always exits with status 0.

Known bugs

None.

Author(s)

History

Target users

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