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Human nucleosomes: special role of CG dinucleotides and Alu-nucleosomes.

Bettecken T, Frenkel ZM, Trifonov EN - BMC Genomics (2011)

Bottom Line: When analyzing the human genome sequence with the positional autocorrelation method, we found that only the dinucleotide CG shows the 10.4 base periodicity, which is indicative of the presence of nucleosomes.This is further confirmed by the positions of CG-periodical nucleosomes on Alu sequences.Considering the exceptional role CG dinucleotides play in the nucleosome positioning, we hypothesize that Alu-nucleosomes, especially, those that form tightly positioned runs, could serve as "anchors" in organizing the chromatin in human cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: CAGT-Center for Applied Genotyping, Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, D-80804 Munich, Germany. bettecken@mpipsykl.mpg.de

ABSTRACT

Background: The periodical occurrence of dinucleotides with a period of 10.4 bases now is undeniably a hallmark of nucleosome positioning. Whereas many eukaryotic genomes contain visible and even strong signals for periodic distribution of dinucleotides, the human genome is rather featureless in this respect. The exact sequence features in the human genome that govern the nucleosome positioning remain largely unknown.

Results: When analyzing the human genome sequence with the positional autocorrelation method, we found that only the dinucleotide CG shows the 10.4 base periodicity, which is indicative of the presence of nucleosomes. There is a high occurrence of CG dinucleotides that are either 31 (10.4 × 3) or 62 (10.4 × 6) base pairs apart from one another - a sequence bias known to be characteristic of Alu-sequences. In a similar analysis with repetitive sequences removed, peaks of repeating CG motifs can be seen at positions 10, 21 and 31, the nearest integers of multiples of 10.4.

Conclusions: Although the CG dinucleotides are dominant, other elements of the standard nucleosome positioning pattern are present in the human genome as well.The positional autocorrelation analysis of the human genome demonstrates that the CG dinucleotide is, indeed, one visible element of the human nucleosome positioning pattern, which appears both in Alu sequences and in sequences without repeats. The dominant role that CG dinucleotides play in organizing human chromatin is to indicate the involvement of human nucleosomes in tuning the regulation of gene expression and chromatin structure, which is very likely due to cytosine-methylation/-demethylation in CG dinucleotides contained in the human nucleosomes. This is further confirmed by the positions of CG-periodical nucleosomes on Alu sequences. Alu repeats appear as monomers, dimers and trimers, harboring two to six nucleosomes in a run. Considering the exceptional role CG dinucleotides play in the nucleosome positioning, we hypothesize that Alu-nucleosomes, especially, those that form tightly positioned runs, could serve as "anchors" in organizing the chromatin in human cells.

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Distances between Alu-repeats in the human genome. Histogram presentation of distances between Alu-repeats (head to head).
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Figure 3: Distances between Alu-repeats in the human genome. Histogram presentation of distances between Alu-repeats (head to head).

Mentions: The role of such hypothetical "anchors" in human chromatin may be played by the nucleosomes positioned on the Alu-sequences. The Alu-sequences contain the CG dinucleotides 31-32 bases apart, that is, at multiples of the nucleosome DNA period [16]. As periodical positioning of CG dinucleotides is an important component of the nucleosome positioning pattern [7], the Alu-sequences could be very well suited for nucleosome formation. Such nucleosomes are, indeed, observed experimentally [20,21]. Moreover, it has been demonstrated recently that the Alu-sequences have influence on the positioning of neighboring nucleosomes [22]. Size-wise, every Alu-sequence may harbor two nucleosomes. However, the Alu-sequences often appear also as tandem dimers and even trimers. In Figure 3, the histogram of distances between the Alu-repeats is shown. Two peaks are observed, at positions ~310 and ~620, corresponding to Alu-dimers and trimers, respectively. The tandem dimers (trimers) of Alu-sequences would contain four (six) nucleosomes each. Such "frozen" combinations of two, four or more tandem nucleosomes, additionally stabilized by their periodical arrangement, could presumably act as those hypothetical anchors. According to our calculations, the human genome contains a total of 1.16 million of such hypothetical Alu-anchors, of which 1,020,000 are singular repeats, 116,000 are dimers and 18,000 are trimers. This corresponds to an average spacer between the Alu sequences or Alu sequence clusters of about 2300 base pairs (tail to head), space enough to accommodate 10-15 nucleosomes. At this point, we would like to propose that repeat sequences in general may well have such a chromatin organizing function. The (19)n and (35)n tandem repeats of C. elegans [23], which contain the standard nucleosome positioning pattern AAATTTCCGG would be sites of formation of strong nucleosomes if our hypothesis holds. Tandemly repeating α-satellite sequences of primates carrying nucleosomes [24] and mouse 234-base satellite nucleosomes [25] could serve as two more examples of potential chromatin anchors.


Human nucleosomes: special role of CG dinucleotides and Alu-nucleosomes.

Bettecken T, Frenkel ZM, Trifonov EN - BMC Genomics (2011)

Distances between Alu-repeats in the human genome. Histogram presentation of distances between Alu-repeats (head to head).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3117857&req=5

Figure 3: Distances between Alu-repeats in the human genome. Histogram presentation of distances between Alu-repeats (head to head).
Mentions: The role of such hypothetical "anchors" in human chromatin may be played by the nucleosomes positioned on the Alu-sequences. The Alu-sequences contain the CG dinucleotides 31-32 bases apart, that is, at multiples of the nucleosome DNA period [16]. As periodical positioning of CG dinucleotides is an important component of the nucleosome positioning pattern [7], the Alu-sequences could be very well suited for nucleosome formation. Such nucleosomes are, indeed, observed experimentally [20,21]. Moreover, it has been demonstrated recently that the Alu-sequences have influence on the positioning of neighboring nucleosomes [22]. Size-wise, every Alu-sequence may harbor two nucleosomes. However, the Alu-sequences often appear also as tandem dimers and even trimers. In Figure 3, the histogram of distances between the Alu-repeats is shown. Two peaks are observed, at positions ~310 and ~620, corresponding to Alu-dimers and trimers, respectively. The tandem dimers (trimers) of Alu-sequences would contain four (six) nucleosomes each. Such "frozen" combinations of two, four or more tandem nucleosomes, additionally stabilized by their periodical arrangement, could presumably act as those hypothetical anchors. According to our calculations, the human genome contains a total of 1.16 million of such hypothetical Alu-anchors, of which 1,020,000 are singular repeats, 116,000 are dimers and 18,000 are trimers. This corresponds to an average spacer between the Alu sequences or Alu sequence clusters of about 2300 base pairs (tail to head), space enough to accommodate 10-15 nucleosomes. At this point, we would like to propose that repeat sequences in general may well have such a chromatin organizing function. The (19)n and (35)n tandem repeats of C. elegans [23], which contain the standard nucleosome positioning pattern AAATTTCCGG would be sites of formation of strong nucleosomes if our hypothesis holds. Tandemly repeating α-satellite sequences of primates carrying nucleosomes [24] and mouse 234-base satellite nucleosomes [25] could serve as two more examples of potential chromatin anchors.

Bottom Line: When analyzing the human genome sequence with the positional autocorrelation method, we found that only the dinucleotide CG shows the 10.4 base periodicity, which is indicative of the presence of nucleosomes.This is further confirmed by the positions of CG-periodical nucleosomes on Alu sequences.Considering the exceptional role CG dinucleotides play in the nucleosome positioning, we hypothesize that Alu-nucleosomes, especially, those that form tightly positioned runs, could serve as "anchors" in organizing the chromatin in human cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: CAGT-Center for Applied Genotyping, Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, D-80804 Munich, Germany. bettecken@mpipsykl.mpg.de

ABSTRACT

Background: The periodical occurrence of dinucleotides with a period of 10.4 bases now is undeniably a hallmark of nucleosome positioning. Whereas many eukaryotic genomes contain visible and even strong signals for periodic distribution of dinucleotides, the human genome is rather featureless in this respect. The exact sequence features in the human genome that govern the nucleosome positioning remain largely unknown.

Results: When analyzing the human genome sequence with the positional autocorrelation method, we found that only the dinucleotide CG shows the 10.4 base periodicity, which is indicative of the presence of nucleosomes. There is a high occurrence of CG dinucleotides that are either 31 (10.4 × 3) or 62 (10.4 × 6) base pairs apart from one another - a sequence bias known to be characteristic of Alu-sequences. In a similar analysis with repetitive sequences removed, peaks of repeating CG motifs can be seen at positions 10, 21 and 31, the nearest integers of multiples of 10.4.

Conclusions: Although the CG dinucleotides are dominant, other elements of the standard nucleosome positioning pattern are present in the human genome as well.The positional autocorrelation analysis of the human genome demonstrates that the CG dinucleotide is, indeed, one visible element of the human nucleosome positioning pattern, which appears both in Alu sequences and in sequences without repeats. The dominant role that CG dinucleotides play in organizing human chromatin is to indicate the involvement of human nucleosomes in tuning the regulation of gene expression and chromatin structure, which is very likely due to cytosine-methylation/-demethylation in CG dinucleotides contained in the human nucleosomes. This is further confirmed by the positions of CG-periodical nucleosomes on Alu sequences. Alu repeats appear as monomers, dimers and trimers, harboring two to six nucleosomes in a run. Considering the exceptional role CG dinucleotides play in the nucleosome positioning, we hypothesize that Alu-nucleosomes, especially, those that form tightly positioned runs, could serve as "anchors" in organizing the chromatin in human cells.

Show MeSH