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A diverse epigenetic landscape at human exons with implication for expression.

Singer M, Kosti I, Pachter L, Mandel-Gutfreund Y - Nucleic Acids Res. (2015)

Bottom Line: Consistent with previous work we found that intragenic methylation is positively correlated with gene expression and that exons are more highly methylated than their neighboring intronic environment.Specifically, we demonstrate that hypo-methylated exons at highly expressed genes are associated with open chromatin and have a characteristic histone code comprised of significantly high levels of histone markings.In particular our results reveal a previously unrecognized diverse and complex role of the epigenetic landscape within the gene body.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science, University of California at Berkeley, Berkeley, CA 94720 USA.

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The difference in methylation between exons and introns is exon-specific. (a) Distribution of methylation rates at exons and their flanking upstream and downstream intron regions shown for all exons (left) the bottom 20th percentile of expression (middle) and the top 20th percentile of expression (right). The thick black lines mark medians, and the surrounding rectangles mark the range of the first and third quartiles. (b) The differences of the methylation rates between the exons and their upstream and downstream flanking intron regions are plotted for all considered exons (left), the bottom 20-th percentile of expression (middle), and the top 20-h percentile of expression (right).
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Figure 2: The difference in methylation between exons and introns is exon-specific. (a) Distribution of methylation rates at exons and their flanking upstream and downstream intron regions shown for all exons (left) the bottom 20th percentile of expression (middle) and the top 20th percentile of expression (right). The thick black lines mark medians, and the surrounding rectangles mark the range of the first and third quartiles. (b) The differences of the methylation rates between the exons and their upstream and downstream flanking intron regions are plotted for all considered exons (left), the bottom 20-th percentile of expression (middle), and the top 20-h percentile of expression (right).

Mentions: We compared the methylation rates at exons to the methylation rates at the upstream and downstream flanking intronic regions (200 nucleotides upstream the 3′ splice site and 200 nucleotides downstream the 5′ splice site). As expected from previous studies (3,14,16,44) and from the positive correlation aforementioned, we can clearly see that overall the highly expressed exons are highly methylated relative to the low expressed exons (Figure 2a). Furthermore, in accordance with previous studies (3,30,31), we found that exons tend to be more methylated than the surrounding intron regions (Figure 2a, P-value = 5.2e−19, see Materials and Methods section). When considering independently the subsets of high expressed (top 20th percentile) and low expressed exons (bottom 20th percentile), the methylation levels of both exons and introns in the high expression set were significantly higher than in the low expression set (Figure 2a, P-value < 2.2e−16, Wilcoxon rank sum test, for the exon regions and the upstream and downstream flanking regions). By quintile measurements with a 90% cutoff on the sets of low and high expressed exons we observed that 38% of low expressed exons have lower methylation than 90% of the high expressed exons, and 36% of the high expressed exons have higher methylation than 90% of the low expressed exons.


A diverse epigenetic landscape at human exons with implication for expression.

Singer M, Kosti I, Pachter L, Mandel-Gutfreund Y - Nucleic Acids Res. (2015)

The difference in methylation between exons and introns is exon-specific. (a) Distribution of methylation rates at exons and their flanking upstream and downstream intron regions shown for all exons (left) the bottom 20th percentile of expression (middle) and the top 20th percentile of expression (right). The thick black lines mark medians, and the surrounding rectangles mark the range of the first and third quartiles. (b) The differences of the methylation rates between the exons and their upstream and downstream flanking intron regions are plotted for all considered exons (left), the bottom 20-th percentile of expression (middle), and the top 20-h percentile of expression (right).
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Related In: Results  -  Collection

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Figure 2: The difference in methylation between exons and introns is exon-specific. (a) Distribution of methylation rates at exons and their flanking upstream and downstream intron regions shown for all exons (left) the bottom 20th percentile of expression (middle) and the top 20th percentile of expression (right). The thick black lines mark medians, and the surrounding rectangles mark the range of the first and third quartiles. (b) The differences of the methylation rates between the exons and their upstream and downstream flanking intron regions are plotted for all considered exons (left), the bottom 20-th percentile of expression (middle), and the top 20-h percentile of expression (right).
Mentions: We compared the methylation rates at exons to the methylation rates at the upstream and downstream flanking intronic regions (200 nucleotides upstream the 3′ splice site and 200 nucleotides downstream the 5′ splice site). As expected from previous studies (3,14,16,44) and from the positive correlation aforementioned, we can clearly see that overall the highly expressed exons are highly methylated relative to the low expressed exons (Figure 2a). Furthermore, in accordance with previous studies (3,30,31), we found that exons tend to be more methylated than the surrounding intron regions (Figure 2a, P-value = 5.2e−19, see Materials and Methods section). When considering independently the subsets of high expressed (top 20th percentile) and low expressed exons (bottom 20th percentile), the methylation levels of both exons and introns in the high expression set were significantly higher than in the low expression set (Figure 2a, P-value < 2.2e−16, Wilcoxon rank sum test, for the exon regions and the upstream and downstream flanking regions). By quintile measurements with a 90% cutoff on the sets of low and high expressed exons we observed that 38% of low expressed exons have lower methylation than 90% of the high expressed exons, and 36% of the high expressed exons have higher methylation than 90% of the low expressed exons.

Bottom Line: Consistent with previous work we found that intragenic methylation is positively correlated with gene expression and that exons are more highly methylated than their neighboring intronic environment.Specifically, we demonstrate that hypo-methylated exons at highly expressed genes are associated with open chromatin and have a characteristic histone code comprised of significantly high levels of histone markings.In particular our results reveal a previously unrecognized diverse and complex role of the epigenetic landscape within the gene body.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science, University of California at Berkeley, Berkeley, CA 94720 USA.

Show MeSH