marscan 



Function

   Finds MAR/SAR sites in nucleic sequences

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

   Here is a sample session with marscan


% marscan 
Finds MAR/SAR sites in nucleic sequences
Input nucleotide sequence(s): tembl:u01317
Output report [u01317.marscan]: 

   Go to the input files for this example
   Go to the output files for this example

Command line arguments

   Standard (Mandatory) qualifiers:
  [-sequence]          seqall     Nucleotide sequence(s) filename and optional
                                  format, or reference (input USA)
  [-outfile]           report     [*.marscan] File for output of MAR/SAR
                                  recognition signature (MRS) regions. This
                                  contains details of the MRS in normal GFF
                                  format. The MRS consists of two recognition
                                  sites, one of 8 bp and one of 16 bp on
                                  either sense strand of the genomic DNA,
                                  within 200 bp of each other.

   Additional (Optional) qualifiers: (none)
   Advanced (Unprompted) qualifiers: (none)
   Associated qualifiers:

   "-sequence" associated qualifiers
   -sbegin1            integer    Start of each sequence to be used
   -send1              integer    End of each sequence to be used
   -sreverse1          boolean    Reverse (if DNA)
   -sask1              boolean    Ask for begin/end/reverse
   -snucleotide1       boolean    Sequence is nucleotide
   -sprotein1          boolean    Sequence is protein
   -slower1            boolean    Make lower case
   -supper1            boolean    Make upper case
   -sformat1           string     Input sequence format
   -sdbname1           string     Database name
   -sid1               string     Entryname
   -ufo1               string     UFO features
   -fformat1           string     Features format
   -fopenfile1         string     Features file name

   "-outfile" associated qualifiers
   -rformat2           string     Report format
   -rname2             string     Base file name
   -rextension2        string     File name extension
   -rdirectory2        string     Output directory
   -raccshow2          boolean    Show accession number in the report
   -rdesshow2          boolean    Show description in the report
   -rscoreshow2        boolean    Show the score in the report
   -rusashow2          boolean    Show the full USA in the report
   -rmaxall2           integer    Maximum total hits to report
   -rmaxseq2           integer    Maximum hits to report for one sequence

   General qualifiers:
   -auto               boolean    Turn off prompts
   -stdout             boolean    Write standard output
   -filter             boolean    Read standard input, write standard output
   -options            boolean    Prompt for standard and additional values
   -debug              boolean    Write debug output to program.dbg
   -verbose            boolean    Report some/full command line options
   -help               boolean    Report command line options. More
                                  information on associated and general
                                  qualifiers can be found with -help -verbose
   -warning            boolean    Report warnings
   -error              boolean    Report errors
   -fatal              boolean    Report fatal errors
   -die                boolean    Report dying program messages

Input file format

   marscan reads a normal genomic DNA USA.

  Input files for usage example

   'tembl:u01317' is a sequence entry in the example nucleic acid
   database 'tembl'

  Database entry: tembl:u01317

ID   U01317; SV 1; linear; genomic DNA; STD; HUM; 73308 BP.
XX
AC   U01317; J00093-J00094; J00096; J00158-J00175; J00177-J00179; K01239;
AC   K01890; K02544; M18047; M19067; M24868; M24886;
XX
DT   19-MAR-1994 (Rel. 39, Created)
DT   14-NOV-2006 (Rel. 89, Last updated, Version 34)
XX
DE   Human beta globin region on chromosome 11.
XX
KW   allelic variation; alternate cap site; Alu repeat; beta-1 pseudogene;
KW   beta-globin; delta-globin; epsilon-globin; gamma-globin; gene duplication;
KW   globin; HPFH; KpnI repetitive sequence; polymorphism; promoter mutation;
KW   pseudogene; repetitive sequence; RNA polymerase III; thalassemia.
XX
OS   Homo sapiens (human)
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia
;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
XX
RN   [1]
RP   62409-62631, 63482-63610
RX   PUBMED; 4135409.
RA   Marotta C.A., Forget B.G., Weissman S.M., Verma I.M., McCaffrey R.P.,
RA   Baltimore D.;
RT   "Nucleotide sequences of human globin messenger RNA";
RL   Proc. Natl. Acad. Sci. U.S.A. 71(6):2300-2304(1974).
XX
RN   [2]
RP   63602-63646
RX   PUBMED; 1059150.
RA   Forget B.G., Marotta C.A., Weissman S.M., Cohen-Solal M.;
RT   "Nucleotide sequences of the 3'-terminal untranslated region of messenger
RT   RNA for human beta globin chain";
RL   Proc. Natl. Acad. Sci. U.S.A. 72(9):3614-3618(1975).
XX
RN   [3]
RP   63593-63626
RX   PUBMED; 788834.
RA   Proudfoot N.J., Brownlee G.G.;
RT   "Nucleotide sequences of globin messenger RNA";
RL   Br. Med. Bull. 32(3):251-256(1976).
XX
RN   [4]
RP   63673-63743
RX   DOI; 10.1016/0092-8674(76)90137-9.
RX   PUBMED; 1035137.
RA   Proudfoot N.J., Longley J.I.;
RT   "The 3' terminal sequences of human alpha and beta globin messenger RNAs:
RT   comparison with rabbit globin messenger RNA";


  [Part of this file has been deleted for brevity]

     aaaggggaga agaatcaaat agacgcaata aaaaatgaca cggggtatca ccactgatcc     7038
0
     cacagaaata caaactaccg tcagagaata ctataaacac ctctacgcaa ataaactaga     7044
0
     aaatctagaa gaaatggata aattcctcga cacatacact ctgccaagac taaaccagga     7050
0
     agaagttgta tctctgaata gaccaataac aggctctgaa attgaggcaa taattaatag     7056
0
     cttatcaacc aaaaaaagtc cgggaccagt aggattcata gccgaattct accagaggta     7062
0
     caaggaggag ctggtaccat tccttctgaa actattccaa tcaatagaaa aagagggaat     7068
0
     cctccctaac tcattttatg aggccagcat catcctgata ccaaagcctg acagagacac     7074
0
     aacaaaaaaa gagaatgtta caccaatatc cttgatgaac atcgatgcaa aaatcctcaa     7080
0
     taaaatactg gcaaactgaa tccagcagca catcaaaaag cttatcctcc atgatcaagt     7086
0
     gggcttcatc cctgccatgc aaggctggtt caacatacga aatcaataaa cataatccag     7092
0
     catataaaca gaaccaaaga cacaaaccat atgattatct caatagatgc agaaaaggcc     7098
0
     tttgacaaaa ttcaacaatg cttcatgcta aaaactctca ataaattagg tattgatggg     7104
0
     acatatctca aaataataag agctatctat gacaaaccca cagccaatat catactgagt     7110
0
     ggacaaaaac tggaagcatt ccctttgaaa actggcacaa ggcagggatg ccctctctca     7116
0
     ccactcctat tcaacatagt gttggaagtt ctggccaggg caatcaggca ggagaaggaa     7122
0
     ataaagggca ttcaattagg aaaagaggaa ggtgaaattg tccctgtttg cagatgacat     7128
0
     gattgtatat ctagaaaacc ccattgtctc agcccaaaat ctccttaagc tgataagcaa     7134
0
     cttcagcaaa gtctcaggat ataaaatcag tgtgcaaaaa tcacaagtat tcctatgcac     7140
0
     caataacaga caaacagaga gccaaatcat gagtgaactc ccattcacaa ttgcttcaaa     7146
0
     gagaataaaa tacctaggaa tccaacttac aagggatgtg aaggacctct tcaaggagaa     7152
0
     ctacaaacca ctgctcaatg aaataaaaga ggatacaaac aaatggaaga acattccatg     7158
0
     cttatgggta ggaagaatca tatcgtgaaa atggtcatac tgcccaaggt aatttataga     7164
0
     ttcaatgcca tccccatcaa gctaccaatg actttcttca cagaactgga aaaaactact     7170
0
     ttaaagttca tatggaatca aaaaagagcc cacatcacca aggcaatcct aagccaaaag     7176
0
     aacaaagctg gaggcatcac gctacctgac ttcaaactat actacaatgc tacggtaacc     7182
0
     aaaacagcat ggtactggta ccaaaacaga gatctagacc aatggaacag aacagagccc     7188
0
     tcagaaataa tgccgcatat ctacaactat ccgatctttg acaaacctga gagaaacaag     7194
0
     caatggggaa aggattccct atttaataaa tggtgctggg aaaactggct agccatatgt     7200
0
     agaaagctga aactggatcc ttccttacac cttatacaaa aattaattca agatggatta     7206
0
     aagacttaaa cattagacct aaaaccataa aaaccctaga aaaaaaccta ggcaatacca     7212
0
     ttcaggacat aggcatgggc aaggacttca tgtctaaaac accaaaacga atggcaacaa     7218
0
     aagacaaaat ggacaaacgg gatctaatta aactaaagag cttctgcaca gctaaagaaa     7224
0
     ctaccatcag agtgaacagg caacctacaa aatgggagaa aatttttgca atctactcat     7230
0
     ctgacaaagg gctaatatcc agaatctaca atgaactcaa acaaatttac aagaaaaaac     7236
0
     aaacaacccc atcaaaaagt gggcaaagga tatgaacaga cacttctcaa aagaagacat     7242
0
     ttatgtaatc aaaaaacaca tgaaaaaatg ctcatcatca ctagccatca gagaaatgca     7248
0
     aatcaaaacc acaatgagat accatctcac accagttaga atggcgatca ttaaaaagtc     7254
0
     aggaaacaac aggtgctgga gaggatgtgg agaaacagga acaactttta cactgttggt     7260
0
     gggactgtaa actagttcaa ccattgcgga agtcagtgtg gcaattcctc aggaatctag     7266
0
     aactagaaat accatttgac ccagccatcc cattactggg tagataccca aaggattata     7272
0
     aatcatgctg ctataaagac acatgcacac gtatgtttat tgcagcacta ttcacaatag     7278
0
     caaagacttg gaaccaaccc aaatgtccaa caacgataga ttggattaag aaaatgtggc     7284
0
     acatatacac catggaatac tatgcagcca taaaaaatga tgagttcatg tcctttgtag     7290
0
     ggacatggat gaagctggaa actatcattc tcagcaaact atcacaagga caataaacca     7296
0
     aacaccgcat gttctcactc ataggtggga attgaacaat gagaacacat ggacacatga     7302
0
     agaggaacat cacactctgg ggactgttat ggggtggggg gcaggggcag ggatagcact     7308
0
     aggagatata cctaatgcta aatgacgagt taatgggtgc agcacaccaa catggcacat     7314
0
     gtatacatat ataacaaacc tgccgttgtg cacatgtacc ctaaaacttg aagtataata     7320
0
     ataaaaaaaa gttatcctat taaaactgat ctcacacatc cgtagagcca ttatcaagtc     7326
0
     tttctctttg aaacagacag aaatttagtg ttttctcagt cagttaac                  7330
8
//

Output file format

   The output is a standard EMBOSS report file.

   The results can be output in one of several styles by using the
   command-line qualifier -rformat xxx, where 'xxx' is replaced by the
   name of the required format. The available format names are: embl,
   genbank, gff, pir, swiss, trace, listfile, dbmotif, diffseq, excel,
   feattable, motif, regions, seqtable, simple, srs, table, tagseq

   See: http://emboss.sf.net/docs/themes/ReportFormats.html for further
   information on report formats.

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

  Output files for usage example

  File: u01317.marscan

##gff-version 2.0
##date 2006-07-15
##Type DNA U01317
U01317  marscan misc_signal     2242    2458    0.000   +       .       Sequenc
e "U01317.1" ; note "*type MAR/SAR recognition site (MRS)" ; note "*start8bp 24
51" ; note "*end8bp 2458" ; note "*start16bp 2242" ; note "*end16bp 2257"
U01317  marscan misc_signal     17654   17730   0.000   +       .       Sequenc
e "U01317.2" ; note "*type MAR/SAR recognition site (MRS)" ; note "*start8bp 17
723" ; note "*end8bp 17730" ; note "*start16bp 17654" ; note "*end16bp 17669"
U01317  marscan misc_signal     40956   41123   0.000   +       .       Sequenc
e "U01317.3" ; note "*type MAR/SAR recognition site (MRS)" ; note "*start8bp 40
956" ; note "*end8bp 40963" ; note "*start16bp 41108" ; note "*end16bp 41123"
U01317  marscan misc_signal     42232   42248   0.000   +       .       Sequenc
e "U01317.4" ; note "*type MAR/SAR recognition site (MRS)" ; note "*start8bp 42
232" ; note "*end8bp 42239" ; note "*start16bp 42233" ; note "*end16bp 42248"
U01317  marscan misc_signal     47834   47966   0.000   +       .       Sequenc
e "U01317.5" ; note "*type MAR/SAR recognition site (MRS)" ; note "*start8bp 47
959" ; note "*end8bp 47966" ; note "*start16bp 47834" ; note "*end16bp 47849"
U01317  marscan misc_signal     65112   65146   0.000   +       .       Sequenc
e "U01317.6" ; note "*type MAR/SAR recognition site (MRS)" ; note "*start8bp 65
139" ; note "*end8bp 65146" ; note "*start16bp 65112" ; note "*end16bp 65127"
U01317  marscan misc_signal     65947   65963   0.000   +       .       Sequenc
e "U01317.7" ; note "*type MAR/SAR recognition site (MRS)" ; note "*start8bp 65
947" ; note "*end8bp 65954" ; note "*start16bp 65948" ; note "*end16bp 65963"

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.

See also

   Program name                        Description
   dreg         Regular expression search of a nucleotide sequence
   fuzznuc      Nucleic acid pattern search
   fuzztran     Protein pattern search after translation
   getorf       Finds and extracts open reading frames (ORFs)
   plotorf      Plot potential open reading frames
   showorf      Pretty output of DNA translations
   sixpack      Display a DNA sequence with 6-frame translation and ORFs
   syco         Synonymous codon usage Gribskov statistic plot
   tcode        Fickett TESTCODE statistic to identify protein-coding DNA
   wobble       Wobble base plot

Author(s)

   Gary Williams (gwilliam  rfcgr.mrc.ac.uk)
   MRC Rosalind Franklin Centre for Genomics Research Wellcome Trust
   Genome Campus, Hinxton, Cambridge, CB10 1SB, UK

History

   Written (Jan 2001) - Gary Williams.

   Changed output file to standard EMBOSS report format (April 2002) -
   Peter Rice

Target users

   This program is intended to be used by everyone and everything, from
   naive users to embedded scripts.

Comments

   None