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Outline of a genome navigation system based on the properties of GA-sequences and their flanks.

Albrecht-Buehler G - PLoS ONE (2009)

Bottom Line: Introducing a new method to visualize large stretches of genomic DNA (see Appendix S1) the article reports that most GA-sequences [1] shared chains of tetra-GA-motifs and contained upstream poly(A)-segments.Although not integral parts of them, Alu-elements were found immediately upstream of all human and chimpanzee GA-sequences with an upstream poly(A)-segment.In response, the associated DNA-loop releases its nucleosomes and allows transcription of the target protein to proceed. (4) The Alu-transcripts may help control the general background of protein synthesis proportional to the number of transcriptionally active associated loops, especially in stressed cells. (5) The model offers a new mechanism of co-regulation of protein synthesis based on the shared segments of different GA-sequences.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America. g-buehler@northwestern.edu

ABSTRACT
Introducing a new method to visualize large stretches of genomic DNA (see Appendix S1) the article reports that most GA-sequences [1] shared chains of tetra-GA-motifs and contained upstream poly(A)-segments. Although not integral parts of them, Alu-elements were found immediately upstream of all human and chimpanzee GA-sequences with an upstream poly(A)-segment. The article hypothesizes that genome navigation uses these properties of GA-sequences in the following way. (1) Poly(A) binding proteins interact with the upstream poly(A)-segments and arrange adjacent GA-sequences side-by-side ('GA-ribbon'), while folding the intervening DNA sequences between them into loops ('associated DNA-loops'). (2) Genome navigation uses the GA-ribbon as a search path for specific target genes that is up to 730-fold shorter than the full-length chromosome. (3) As to the specificity of the search, each molecule of a target protein is assumed to catalyze the formation of specific oligomers from a set of transcription factors that recognize tetra-GA-motifs. Their specific combinations of tetra-GA motifs are assumed to be present in the particular GA-sequence whose associated loop contains the gene for the target protein. As long as the target protein is abundant in the cell it produces sufficient numbers of such oligomers which bind to their specific GA-sequences and, thereby, inhibit locally the transcription of the target protein in the associated loop. However, if the amount of target protein drops below a certain threshold, the resultant reduction of specific oligomers leaves the corresponding GA-sequence 'denuded'. In response, the associated DNA-loop releases its nucleosomes and allows transcription of the target protein to proceed. (4) The Alu-transcripts may help control the general background of protein synthesis proportional to the number of transcriptionally active associated loops, especially in stressed cells. (5) The model offers a new mechanism of co-regulation of protein synthesis based on the shared segments of different GA-sequences.

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Side-by-side alignment of consecutive GA-sequences by poly(A) binding proteins (PABP).The GA-sequences (black and white striped segments) are assumed to be sign posts for a searching mechanism that uses their upstream poly(A)-segments (black stretches) as markers for the reading direction and as binding sites for PABPs that link them side-by-side. The intervening stretches of genomic DNA have variable sizes and loop around to the next GA-sequence. The parallel arrangement of GA-sequences is called the ‘GA-ribbon’. The GA-sequences are assumed to be associated with DNA binding proteins that are specific for tetra-GA motifs (not shown; see Fig. 7).
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pone-0004701-g005: Side-by-side alignment of consecutive GA-sequences by poly(A) binding proteins (PABP).The GA-sequences (black and white striped segments) are assumed to be sign posts for a searching mechanism that uses their upstream poly(A)-segments (black stretches) as markers for the reading direction and as binding sites for PABPs that link them side-by-side. The intervening stretches of genomic DNA have variable sizes and loop around to the next GA-sequence. The parallel arrangement of GA-sequences is called the ‘GA-ribbon’. The GA-sequences are assumed to be associated with DNA binding proteins that are specific for tetra-GA motifs (not shown; see Fig. 7).

Mentions: Since all pure GA-sequences of a chromosome are lined up in tandem on the same DNA strand, there is essentially only one non-disruptive way of forcing all of them into a small space, namely by placing the pure GA-sequences side-by-side while folding the intervening stretches of DNA between them into loops (See Fig. 5, Fig. 6).


Outline of a genome navigation system based on the properties of GA-sequences and their flanks.

Albrecht-Buehler G - PLoS ONE (2009)

Side-by-side alignment of consecutive GA-sequences by poly(A) binding proteins (PABP).The GA-sequences (black and white striped segments) are assumed to be sign posts for a searching mechanism that uses their upstream poly(A)-segments (black stretches) as markers for the reading direction and as binding sites for PABPs that link them side-by-side. The intervening stretches of genomic DNA have variable sizes and loop around to the next GA-sequence. The parallel arrangement of GA-sequences is called the ‘GA-ribbon’. The GA-sequences are assumed to be associated with DNA binding proteins that are specific for tetra-GA motifs (not shown; see Fig. 7).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2651618&req=5

pone-0004701-g005: Side-by-side alignment of consecutive GA-sequences by poly(A) binding proteins (PABP).The GA-sequences (black and white striped segments) are assumed to be sign posts for a searching mechanism that uses their upstream poly(A)-segments (black stretches) as markers for the reading direction and as binding sites for PABPs that link them side-by-side. The intervening stretches of genomic DNA have variable sizes and loop around to the next GA-sequence. The parallel arrangement of GA-sequences is called the ‘GA-ribbon’. The GA-sequences are assumed to be associated with DNA binding proteins that are specific for tetra-GA motifs (not shown; see Fig. 7).
Mentions: Since all pure GA-sequences of a chromosome are lined up in tandem on the same DNA strand, there is essentially only one non-disruptive way of forcing all of them into a small space, namely by placing the pure GA-sequences side-by-side while folding the intervening stretches of DNA between them into loops (See Fig. 5, Fig. 6).

Bottom Line: Introducing a new method to visualize large stretches of genomic DNA (see Appendix S1) the article reports that most GA-sequences [1] shared chains of tetra-GA-motifs and contained upstream poly(A)-segments.Although not integral parts of them, Alu-elements were found immediately upstream of all human and chimpanzee GA-sequences with an upstream poly(A)-segment.In response, the associated DNA-loop releases its nucleosomes and allows transcription of the target protein to proceed. (4) The Alu-transcripts may help control the general background of protein synthesis proportional to the number of transcriptionally active associated loops, especially in stressed cells. (5) The model offers a new mechanism of co-regulation of protein synthesis based on the shared segments of different GA-sequences.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America. g-buehler@northwestern.edu

ABSTRACT
Introducing a new method to visualize large stretches of genomic DNA (see Appendix S1) the article reports that most GA-sequences [1] shared chains of tetra-GA-motifs and contained upstream poly(A)-segments. Although not integral parts of them, Alu-elements were found immediately upstream of all human and chimpanzee GA-sequences with an upstream poly(A)-segment. The article hypothesizes that genome navigation uses these properties of GA-sequences in the following way. (1) Poly(A) binding proteins interact with the upstream poly(A)-segments and arrange adjacent GA-sequences side-by-side ('GA-ribbon'), while folding the intervening DNA sequences between them into loops ('associated DNA-loops'). (2) Genome navigation uses the GA-ribbon as a search path for specific target genes that is up to 730-fold shorter than the full-length chromosome. (3) As to the specificity of the search, each molecule of a target protein is assumed to catalyze the formation of specific oligomers from a set of transcription factors that recognize tetra-GA-motifs. Their specific combinations of tetra-GA motifs are assumed to be present in the particular GA-sequence whose associated loop contains the gene for the target protein. As long as the target protein is abundant in the cell it produces sufficient numbers of such oligomers which bind to their specific GA-sequences and, thereby, inhibit locally the transcription of the target protein in the associated loop. However, if the amount of target protein drops below a certain threshold, the resultant reduction of specific oligomers leaves the corresponding GA-sequence 'denuded'. In response, the associated DNA-loop releases its nucleosomes and allows transcription of the target protein to proceed. (4) The Alu-transcripts may help control the general background of protein synthesis proportional to the number of transcriptionally active associated loops, especially in stressed cells. (5) The model offers a new mechanism of co-regulation of protein synthesis based on the shared segments of different GA-sequences.

Show MeSH
Related in: MedlinePlus