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Determination of enriched histone modifications in non-genic portions of the human genome.

Rosenfeld JA, Wang Z, Schones DE, Zhao K, DeSalle R, Zhang MQ - BMC Genomics (2009)

Bottom Line: Different methylation states of H4K20, H3K9 and H3K27 were found to be enriched in each region relative to the other regions.Finally, we compared the modification patterns in non-genic regions to those at silent genes and genes with higher levels of expression.For H3K27me3, the highest levels are found in silent genes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. rosenfel@cshl.edu

ABSTRACT

Background: Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) has recently been used to identify the modification patterns for the methylation and acetylation of many different histone tails in genes and enhancers.

Results: We have extended the analysis of histone modifications to gene deserts, pericentromeres and subtelomeres. Using data from human CD4+ T cells, we have found that each of these non-genic regions has a particular profile of histone modifications that distinguish it from the other non-coding regions. Different methylation states of H4K20, H3K9 and H3K27 were found to be enriched in each region relative to the other regions. These findings indicate that non-genic regions of the genome are variable with respect to histone modification patterns, rather than being monolithic. We furthermore used consensus sequences for unassembled centromeres and telomeres to identify the significant histone modifications in these regions. Finally, we compared the modification patterns in non-genic regions to those at silent genes and genes with higher levels of expression. For all tested methylations with the exception of H3K27me3, the enrichment level of each modification state for silent genes is between that of non-genic regions and expressed genes. For H3K27me3, the highest levels are found in silent genes.

Conclusion: In addition to the histone modification pattern difference between euchromatin and heterochromatin regions, as is illustrated by the enrichment of H3K9me2/3 in non-genic regions while H3K9me1 is enriched at active genes; the chromatin modifications within non-genic (heterochromatin-like) regions (e.g. subtelomeres, pericentromeres and gene deserts) are also quite different.

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Profiles of different levels of methylation for H3K27. The points represent the mean value with the error bars showing the standard error. Each level of methylation of this residue has a distinct profile with the tri-methylation most highly enriched in silent genes. Even though the levels of the three types of H3K27me are indistinguishable in silent genes, the levels of H3K27me3 are clearly higher there than anywhere else. All of the data has been normalized to the number of counts of each modification in the genome, so the genomic average for each mark is 1.
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Figure 4: Profiles of different levels of methylation for H3K27. The points represent the mean value with the error bars showing the standard error. Each level of methylation of this residue has a distinct profile with the tri-methylation most highly enriched in silent genes. Even though the levels of the three types of H3K27me are indistinguishable in silent genes, the levels of H3K27me3 are clearly higher there than anywhere else. All of the data has been normalized to the number of counts of each modification in the genome, so the genomic average for each mark is 1.

Mentions: Different methylation states of H3K27 are found to be significant in distinct parts of the genome (Table 2). Because of this variation, we wanted to determine how the different modification states are related to genes with different levels of expression. We determined the number of counts for each methylation state of H3K27me3 in each type of region in the genome. The resulting plots are shown in Figure 4.


Determination of enriched histone modifications in non-genic portions of the human genome.

Rosenfeld JA, Wang Z, Schones DE, Zhao K, DeSalle R, Zhang MQ - BMC Genomics (2009)

Profiles of different levels of methylation for H3K27. The points represent the mean value with the error bars showing the standard error. Each level of methylation of this residue has a distinct profile with the tri-methylation most highly enriched in silent genes. Even though the levels of the three types of H3K27me are indistinguishable in silent genes, the levels of H3K27me3 are clearly higher there than anywhere else. All of the data has been normalized to the number of counts of each modification in the genome, so the genomic average for each mark is 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2667539&req=5

Figure 4: Profiles of different levels of methylation for H3K27. The points represent the mean value with the error bars showing the standard error. Each level of methylation of this residue has a distinct profile with the tri-methylation most highly enriched in silent genes. Even though the levels of the three types of H3K27me are indistinguishable in silent genes, the levels of H3K27me3 are clearly higher there than anywhere else. All of the data has been normalized to the number of counts of each modification in the genome, so the genomic average for each mark is 1.
Mentions: Different methylation states of H3K27 are found to be significant in distinct parts of the genome (Table 2). Because of this variation, we wanted to determine how the different modification states are related to genes with different levels of expression. We determined the number of counts for each methylation state of H3K27me3 in each type of region in the genome. The resulting plots are shown in Figure 4.

Bottom Line: Different methylation states of H4K20, H3K9 and H3K27 were found to be enriched in each region relative to the other regions.Finally, we compared the modification patterns in non-genic regions to those at silent genes and genes with higher levels of expression.For H3K27me3, the highest levels are found in silent genes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. rosenfel@cshl.edu

ABSTRACT

Background: Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) has recently been used to identify the modification patterns for the methylation and acetylation of many different histone tails in genes and enhancers.

Results: We have extended the analysis of histone modifications to gene deserts, pericentromeres and subtelomeres. Using data from human CD4+ T cells, we have found that each of these non-genic regions has a particular profile of histone modifications that distinguish it from the other non-coding regions. Different methylation states of H4K20, H3K9 and H3K27 were found to be enriched in each region relative to the other regions. These findings indicate that non-genic regions of the genome are variable with respect to histone modification patterns, rather than being monolithic. We furthermore used consensus sequences for unassembled centromeres and telomeres to identify the significant histone modifications in these regions. Finally, we compared the modification patterns in non-genic regions to those at silent genes and genes with higher levels of expression. For all tested methylations with the exception of H3K27me3, the enrichment level of each modification state for silent genes is between that of non-genic regions and expressed genes. For H3K27me3, the highest levels are found in silent genes.

Conclusion: In addition to the histone modification pattern difference between euchromatin and heterochromatin regions, as is illustrated by the enrichment of H3K9me2/3 in non-genic regions while H3K9me1 is enriched at active genes; the chromatin modifications within non-genic (heterochromatin-like) regions (e.g. subtelomeres, pericentromeres and gene deserts) are also quite different.

Show MeSH