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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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Predominance of tetra-GA motifs in the pure GA-sequences of human chr. 1 as demonstrated by the GPxI method.The highlighted field in the left hand panels are enlarged in the right hand panels.(Scales: 50[b]/division). a. The GPxI of a computer-constructed DNA file consisting of random sequences of G (white pixels) and A (black pixels). Therefore, no pixels with other gray-values are visible. The randomness is of the sequences is expressed by the lack of any detectable patterns. b. GPxI of the end-to-end concatenated pure GA-sequences of human chr. 1 shows clearly a number of patterns. Although different, they seem to share a periodicity of 4. c., d. Use of a modified Markham rotation [3] to demonstrate the prevalence of the 4-periodicity. In panel c the GPxI of panel b is superimposed on itself although frame shifted by 2 bases. The result is a rather featureless gray image. In panel d the applied frame shift is 4. The result is the almost identical re-appearance of the original GPxI, indicating that a frame-shift of 4 reinforces the prevalent patterns.
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pone-0004701-g002: Predominance of tetra-GA motifs in the pure GA-sequences of human chr. 1 as demonstrated by the GPxI method.The highlighted field in the left hand panels are enlarged in the right hand panels.(Scales: 50[b]/division). a. The GPxI of a computer-constructed DNA file consisting of random sequences of G (white pixels) and A (black pixels). Therefore, no pixels with other gray-values are visible. The randomness is of the sequences is expressed by the lack of any detectable patterns. b. GPxI of the end-to-end concatenated pure GA-sequences of human chr. 1 shows clearly a number of patterns. Although different, they seem to share a periodicity of 4. c., d. Use of a modified Markham rotation [3] to demonstrate the prevalence of the 4-periodicity. In panel c the GPxI of panel b is superimposed on itself although frame shifted by 2 bases. The result is a rather featureless gray image. In panel d the applied frame shift is 4. The result is the almost identical re-appearance of the original GPxI, indicating that a frame-shift of 4 reinforces the prevalent patterns.

Mentions: Concatenating end-to-end all 1667 pure GA-sequences of human chr.1 yielded the GPxI shown in Figure 2b. The comparison with a computer-constructed random GA-sequence file (Figure 2a), confirmed that the pure GA-sequences contain many repetitive patterns.


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

Albrecht-Buehler G - PLoS ONE (2009)

Predominance of tetra-GA motifs in the pure GA-sequences of human chr. 1 as demonstrated by the GPxI method.The highlighted field in the left hand panels are enlarged in the right hand panels.(Scales: 50[b]/division). a. The GPxI of a computer-constructed DNA file consisting of random sequences of G (white pixels) and A (black pixels). Therefore, no pixels with other gray-values are visible. The randomness is of the sequences is expressed by the lack of any detectable patterns. b. GPxI of the end-to-end concatenated pure GA-sequences of human chr. 1 shows clearly a number of patterns. Although different, they seem to share a periodicity of 4. c., d. Use of a modified Markham rotation [3] to demonstrate the prevalence of the 4-periodicity. In panel c the GPxI of panel b is superimposed on itself although frame shifted by 2 bases. The result is a rather featureless gray image. In panel d the applied frame shift is 4. The result is the almost identical re-appearance of the original GPxI, indicating that a frame-shift of 4 reinforces the prevalent patterns.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2651618&req=5

pone-0004701-g002: Predominance of tetra-GA motifs in the pure GA-sequences of human chr. 1 as demonstrated by the GPxI method.The highlighted field in the left hand panels are enlarged in the right hand panels.(Scales: 50[b]/division). a. The GPxI of a computer-constructed DNA file consisting of random sequences of G (white pixels) and A (black pixels). Therefore, no pixels with other gray-values are visible. The randomness is of the sequences is expressed by the lack of any detectable patterns. b. GPxI of the end-to-end concatenated pure GA-sequences of human chr. 1 shows clearly a number of patterns. Although different, they seem to share a periodicity of 4. c., d. Use of a modified Markham rotation [3] to demonstrate the prevalence of the 4-periodicity. In panel c the GPxI of panel b is superimposed on itself although frame shifted by 2 bases. The result is a rather featureless gray image. In panel d the applied frame shift is 4. The result is the almost identical re-appearance of the original GPxI, indicating that a frame-shift of 4 reinforces the prevalent patterns.
Mentions: Concatenating end-to-end all 1667 pure GA-sequences of human chr.1 yielded the GPxI shown in Figure 2b. The comparison with a computer-constructed random GA-sequence file (Figure 2a), confirmed that the pure GA-sequences contain many repetitive patterns.

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