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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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Typical appearance of the GPxI of the GA-complexes ( = upstream flank of 400 [b]+GA-sequence+downstream flank of 400 [b]) of human chromosomes.The GA-complexes are vertically aligned with the upstream ends of their GA-sequences. While the ends of all upstream flanks are automatically aligned, because they extend the same distance from the GA-sequences, the ends of the downstream flanks are not and appear frayed, as the length of each GA-sequence varies. The aligned GA-sequences in their natural order of occurrences in the chromosome are labeled as ‘GA-ribbon’. a. GPxI of the first 1000 GA-complexes of human chr.1 in their natural order of occurrence in the chromosome. Note the appearance of the ‘upstream stripes’ (see text) in the aligned upstream flanks and the predominantly black ( = poly-A) upstream beginnings of the aligned GA-sequences.(Scale: 50 [b]/division). b. Enlargement of the frame shown in panel a. Arrow points to the border between upstream flank and GA-sequence. By definition, it consists of T’’s or C's. (Scale: 50 bases).
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pone-0004701-g001: Typical appearance of the GPxI of the GA-complexes ( = upstream flank of 400 [b]+GA-sequence+downstream flank of 400 [b]) of human chromosomes.The GA-complexes are vertically aligned with the upstream ends of their GA-sequences. While the ends of all upstream flanks are automatically aligned, because they extend the same distance from the GA-sequences, the ends of the downstream flanks are not and appear frayed, as the length of each GA-sequence varies. The aligned GA-sequences in their natural order of occurrences in the chromosome are labeled as ‘GA-ribbon’. a. GPxI of the first 1000 GA-complexes of human chr.1 in their natural order of occurrence in the chromosome. Note the appearance of the ‘upstream stripes’ (see text) in the aligned upstream flanks and the predominantly black ( = poly-A) upstream beginnings of the aligned GA-sequences.(Scale: 50 [b]/division). b. Enlargement of the frame shown in panel a. Arrow points to the border between upstream flank and GA-sequence. By definition, it consists of T’’s or C's. (Scale: 50 bases).

Mentions: The GPxI of the first 1,100 GA-complexes of human chr. 1 displayed in their natural order of occurrence are shown in Fig. 1a. The upstream ( = left hand) ends of all GA-complexes were aligned in the vertical direction, which automatically also aligned the upstream ends of the GA-sequences. In contrast, the downstream flanks were not aligned in this GPxI, because the lengths of the pure GA-sequence were variable [see 1], thus pushing the ends of the downstream flanks to variable positions.


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

Albrecht-Buehler G - PLoS ONE (2009)

Typical appearance of the GPxI of the GA-complexes ( = upstream flank of 400 [b]+GA-sequence+downstream flank of 400 [b]) of human chromosomes.The GA-complexes are vertically aligned with the upstream ends of their GA-sequences. While the ends of all upstream flanks are automatically aligned, because they extend the same distance from the GA-sequences, the ends of the downstream flanks are not and appear frayed, as the length of each GA-sequence varies. The aligned GA-sequences in their natural order of occurrences in the chromosome are labeled as ‘GA-ribbon’. a. GPxI of the first 1000 GA-complexes of human chr.1 in their natural order of occurrence in the chromosome. Note the appearance of the ‘upstream stripes’ (see text) in the aligned upstream flanks and the predominantly black ( = poly-A) upstream beginnings of the aligned GA-sequences.(Scale: 50 [b]/division). b. Enlargement of the frame shown in panel a. Arrow points to the border between upstream flank and GA-sequence. By definition, it consists of T’’s or C's. (Scale: 50 bases).
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Related In: Results  -  Collection

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pone-0004701-g001: Typical appearance of the GPxI of the GA-complexes ( = upstream flank of 400 [b]+GA-sequence+downstream flank of 400 [b]) of human chromosomes.The GA-complexes are vertically aligned with the upstream ends of their GA-sequences. While the ends of all upstream flanks are automatically aligned, because they extend the same distance from the GA-sequences, the ends of the downstream flanks are not and appear frayed, as the length of each GA-sequence varies. The aligned GA-sequences in their natural order of occurrences in the chromosome are labeled as ‘GA-ribbon’. a. GPxI of the first 1000 GA-complexes of human chr.1 in their natural order of occurrence in the chromosome. Note the appearance of the ‘upstream stripes’ (see text) in the aligned upstream flanks and the predominantly black ( = poly-A) upstream beginnings of the aligned GA-sequences.(Scale: 50 [b]/division). b. Enlargement of the frame shown in panel a. Arrow points to the border between upstream flank and GA-sequence. By definition, it consists of T’’s or C's. (Scale: 50 bases).
Mentions: The GPxI of the first 1,100 GA-complexes of human chr. 1 displayed in their natural order of occurrence are shown in Fig. 1a. The upstream ( = left hand) ends of all GA-complexes were aligned in the vertical direction, which automatically also aligned the upstream ends of the GA-sequences. In contrast, the downstream flanks were not aligned in this GPxI, because the lengths of the pure GA-sequence were variable [see 1], thus pushing the ends of the downstream flanks to variable positions.

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