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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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Identity between upstream stripes and Alu-sequences and their expression as a function of upstream poly(A)-segments of the GA-sequences.The GPxIs show portions of the GA-complexes of human chr.1 after sorting them by the decreasing size of poly(A)-segments at the upstream end of the GA-sequences. The aligned GA-sequences are labeled as ‘GA-alignment’ because they are not depicted in their natural order. (Scale: 50[b]/division). a. Absence of upstream stripes wherever the upstream ends of the GA-sequences contained no poly(A)-segments. b. Strong expression of upstream stripes where the GA-sequences ended in large upstream poly(A)-segments (black stretches). c. GPxI of the matches of the Alu-consensus sequence cited in the text and their 400 base large up- and down-stream flanks found in human chr.1. Note, the Alu-pattern extends upstream beyond the limit of the consensus sequences. Numerous point mutations can be seen as individual pixels that have a different gray value than the consensus pattern above and below. Furthermore, each Alu-sequences seems to terminate downstream in a stretch of black pixels, i.e. in a poly(A)-sequence.
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pone-0004701-g004: Identity between upstream stripes and Alu-sequences and their expression as a function of upstream poly(A)-segments of the GA-sequences.The GPxIs show portions of the GA-complexes of human chr.1 after sorting them by the decreasing size of poly(A)-segments at the upstream end of the GA-sequences. The aligned GA-sequences are labeled as ‘GA-alignment’ because they are not depicted in their natural order. (Scale: 50[b]/division). a. Absence of upstream stripes wherever the upstream ends of the GA-sequences contained no poly(A)-segments. b. Strong expression of upstream stripes where the GA-sequences ended in large upstream poly(A)-segments (black stretches). c. GPxI of the matches of the Alu-consensus sequence cited in the text and their 400 base large up- and down-stream flanks found in human chr.1. Note, the Alu-pattern extends upstream beyond the limit of the consensus sequences. Numerous point mutations can be seen as individual pixels that have a different gray value than the consensus pattern above and below. Furthermore, each Alu-sequences seems to terminate downstream in a stretch of black pixels, i.e. in a poly(A)-sequence.

Mentions: The GPxIs generated from the common GA-sequences of human and chimpanzee chromosomes after re-ordering them by the size of their upstream poly(A)-segment confirmed that the upstream poly(A) stretches were required for the appearance of upstream stripes: Whenever the GA-sequences did not end in an upstream poly(A) motif, upstream stripes were not visible in the GA-complex, either (Fig. 4a). In contrast, when the GPxI of a GA-sequence displayed a predominantly black stretch, the upstream stripes were strongly expressed in its upstream flank (Fig. 4b).


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

Albrecht-Buehler G - PLoS ONE (2009)

Identity between upstream stripes and Alu-sequences and their expression as a function of upstream poly(A)-segments of the GA-sequences.The GPxIs show portions of the GA-complexes of human chr.1 after sorting them by the decreasing size of poly(A)-segments at the upstream end of the GA-sequences. The aligned GA-sequences are labeled as ‘GA-alignment’ because they are not depicted in their natural order. (Scale: 50[b]/division). a. Absence of upstream stripes wherever the upstream ends of the GA-sequences contained no poly(A)-segments. b. Strong expression of upstream stripes where the GA-sequences ended in large upstream poly(A)-segments (black stretches). c. GPxI of the matches of the Alu-consensus sequence cited in the text and their 400 base large up- and down-stream flanks found in human chr.1. Note, the Alu-pattern extends upstream beyond the limit of the consensus sequences. Numerous point mutations can be seen as individual pixels that have a different gray value than the consensus pattern above and below. Furthermore, each Alu-sequences seems to terminate downstream in a stretch of black pixels, i.e. in a poly(A)-sequence.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2651618&req=5

pone-0004701-g004: Identity between upstream stripes and Alu-sequences and their expression as a function of upstream poly(A)-segments of the GA-sequences.The GPxIs show portions of the GA-complexes of human chr.1 after sorting them by the decreasing size of poly(A)-segments at the upstream end of the GA-sequences. The aligned GA-sequences are labeled as ‘GA-alignment’ because they are not depicted in their natural order. (Scale: 50[b]/division). a. Absence of upstream stripes wherever the upstream ends of the GA-sequences contained no poly(A)-segments. b. Strong expression of upstream stripes where the GA-sequences ended in large upstream poly(A)-segments (black stretches). c. GPxI of the matches of the Alu-consensus sequence cited in the text and their 400 base large up- and down-stream flanks found in human chr.1. Note, the Alu-pattern extends upstream beyond the limit of the consensus sequences. Numerous point mutations can be seen as individual pixels that have a different gray value than the consensus pattern above and below. Furthermore, each Alu-sequences seems to terminate downstream in a stretch of black pixels, i.e. in a poly(A)-sequence.
Mentions: The GPxIs generated from the common GA-sequences of human and chimpanzee chromosomes after re-ordering them by the size of their upstream poly(A)-segment confirmed that the upstream poly(A) stretches were required for the appearance of upstream stripes: Whenever the GA-sequences did not end in an upstream poly(A) motif, upstream stripes were not visible in the GA-complex, either (Fig. 4a). In contrast, when the GPxI of a GA-sequence displayed a predominantly black stretch, the upstream stripes were strongly expressed in its upstream flank (Fig. 4b).

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