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Epigenetic features are significantly associated with alternative splicing.

Zhou Y, Lu Y, Tian W - BMC Genomics (2012)

Bottom Line: In this study, we discover that a number of epigenetic features, including DNA methylation, nucleosome occupancy, specific histone modifications and protein features, are strongly associated with AS.In addition, we find that the AS types can be classified into two general classes, namely the exon skipping related process (ESRP), and the alternative splice site selection process (ASSP), based on their association levels with the epigenetic features.Our analysis thus suggests that epigenetic features are likely to play important roles in regulating AS.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Genetic Engineering, Institute of Biostatistics, School of Life Science, Fudan University, Shanghai, China.

ABSTRACT

Background: While alternative splicing (AS) contributes greatly to protein diversities, the relationship between various types of AS and epigenetic factors remains largely unknown.

Results: In this study, we discover that a number of epigenetic features, including DNA methylation, nucleosome occupancy, specific histone modifications and protein features, are strongly associated with AS. To further enhance our understanding of the association between these features and AS, we cluster our investigated features based on their association patterns with each AS type into four groups, with H3K36me3, EGR1, GABP, SRF, SIN3A and RNA Pol II grouped together and showing strongest association with AS. In addition, we find that the AS types can be classified into two general classes, namely the exon skipping related process (ESRP), and the alternative splice site selection process (ASSP), based on their association levels with the epigenetic features.

Conclusion: Our analysis thus suggests that epigenetic features are likely to play important roles in regulating AS.

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The association of DNA methylation and nucleosome occupancy with AS. (a) The distribution of genomic CpG dinucleotides level (CG) around the splice sites of different types of AS events. (b) The distribution of DNA methylation level (mCG) around the splice sites of different types of AS events. In both a and b, a sliding window of 147 bp is used for generating the profile for the figure; the x-axis is the position relative to acceptor site (left) and donor site (right); the y-axis is the CG percentage for a and the methylation percentage for b. (c) The distribution of nucleosome occupancy around the splice sites of different types of AS events. In c, no sliding window is used (see Methods for details); the x-axis is as in a, and the y-axis represents the ChIP signal level. (ES (exon skipping), ME (mutually exclusive exon, A5SS (alternative 5' splice site selection) A3SS (alternative 3' splice site selection), IR (intron retention)).
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Figure 1: The association of DNA methylation and nucleosome occupancy with AS. (a) The distribution of genomic CpG dinucleotides level (CG) around the splice sites of different types of AS events. (b) The distribution of DNA methylation level (mCG) around the splice sites of different types of AS events. In both a and b, a sliding window of 147 bp is used for generating the profile for the figure; the x-axis is the position relative to acceptor site (left) and donor site (right); the y-axis is the CG percentage for a and the methylation percentage for b. (c) The distribution of nucleosome occupancy around the splice sites of different types of AS events. In c, no sliding window is used (see Methods for details); the x-axis is as in a, and the y-axis represents the ChIP signal level. (ES (exon skipping), ME (mutually exclusive exon, A5SS (alternative 5' splice site selection) A3SS (alternative 3' splice site selection), IR (intron retention)).

Mentions: We find that ME and ES have significantly lower level of both CG and mCG in the exonic regions (Figure 1a-b). In contrast, IR has significantly higher level of CG in both the exonic and intronic regions; yet, its mCG level in the exonic region is significantly lower while in the intronic region is significantly higher. For both A3SS and A5SS, their associations with CG and mCG are generally not as significant as that with the other types of ASE, though the association is significant in some regions (See Additional file 2 for details). The association patterns of mCG with the ASE in individual cell lines are similar to the above results (Additional file 3).


Epigenetic features are significantly associated with alternative splicing.

Zhou Y, Lu Y, Tian W - BMC Genomics (2012)

The association of DNA methylation and nucleosome occupancy with AS. (a) The distribution of genomic CpG dinucleotides level (CG) around the splice sites of different types of AS events. (b) The distribution of DNA methylation level (mCG) around the splice sites of different types of AS events. In both a and b, a sliding window of 147 bp is used for generating the profile for the figure; the x-axis is the position relative to acceptor site (left) and donor site (right); the y-axis is the CG percentage for a and the methylation percentage for b. (c) The distribution of nucleosome occupancy around the splice sites of different types of AS events. In c, no sliding window is used (see Methods for details); the x-axis is as in a, and the y-axis represents the ChIP signal level. (ES (exon skipping), ME (mutually exclusive exon, A5SS (alternative 5' splice site selection) A3SS (alternative 3' splice site selection), IR (intron retention)).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 1: The association of DNA methylation and nucleosome occupancy with AS. (a) The distribution of genomic CpG dinucleotides level (CG) around the splice sites of different types of AS events. (b) The distribution of DNA methylation level (mCG) around the splice sites of different types of AS events. In both a and b, a sliding window of 147 bp is used for generating the profile for the figure; the x-axis is the position relative to acceptor site (left) and donor site (right); the y-axis is the CG percentage for a and the methylation percentage for b. (c) The distribution of nucleosome occupancy around the splice sites of different types of AS events. In c, no sliding window is used (see Methods for details); the x-axis is as in a, and the y-axis represents the ChIP signal level. (ES (exon skipping), ME (mutually exclusive exon, A5SS (alternative 5' splice site selection) A3SS (alternative 3' splice site selection), IR (intron retention)).
Mentions: We find that ME and ES have significantly lower level of both CG and mCG in the exonic regions (Figure 1a-b). In contrast, IR has significantly higher level of CG in both the exonic and intronic regions; yet, its mCG level in the exonic region is significantly lower while in the intronic region is significantly higher. For both A3SS and A5SS, their associations with CG and mCG are generally not as significant as that with the other types of ASE, though the association is significant in some regions (See Additional file 2 for details). The association patterns of mCG with the ASE in individual cell lines are similar to the above results (Additional file 3).

Bottom Line: In this study, we discover that a number of epigenetic features, including DNA methylation, nucleosome occupancy, specific histone modifications and protein features, are strongly associated with AS.In addition, we find that the AS types can be classified into two general classes, namely the exon skipping related process (ESRP), and the alternative splice site selection process (ASSP), based on their association levels with the epigenetic features.Our analysis thus suggests that epigenetic features are likely to play important roles in regulating AS.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Genetic Engineering, Institute of Biostatistics, School of Life Science, Fudan University, Shanghai, China.

ABSTRACT

Background: While alternative splicing (AS) contributes greatly to protein diversities, the relationship between various types of AS and epigenetic factors remains largely unknown.

Results: In this study, we discover that a number of epigenetic features, including DNA methylation, nucleosome occupancy, specific histone modifications and protein features, are strongly associated with AS. To further enhance our understanding of the association between these features and AS, we cluster our investigated features based on their association patterns with each AS type into four groups, with H3K36me3, EGR1, GABP, SRF, SIN3A and RNA Pol II grouped together and showing strongest association with AS. In addition, we find that the AS types can be classified into two general classes, namely the exon skipping related process (ESRP), and the alternative splice site selection process (ASSP), based on their association levels with the epigenetic features.

Conclusion: Our analysis thus suggests that epigenetic features are likely to play important roles in regulating AS.

Show MeSH