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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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A diagram outlining the analysis that was performed on the data. The diagram uses the example of gene deserts to describe the analysis, but the same techniques were used for pericentromeres, subtelomeres and silent, medium expression and high expression genes.
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Figure 1: A diagram outlining the analysis that was performed on the data. The diagram uses the example of gene deserts to describe the analysis, but the same techniques were used for pericentromeres, subtelomeres and silent, medium expression and high expression genes.

Mentions: To characterize the histone modifications that are enriched in different regions of the genome, we first obtained the locations of each type of region. Our determinations were made based upon gene annotations (see Methods and Figure 1 for details). Pericentromeres were defined for each chromosome as the region between the two genes most proximal to the centromeric gap in the genome assembly. From this region, the 10 kb nearest to each of the genes was removed since it could contain regulatory elements for the genes. Subtelomeres designations from [24] were used as a starting point. If a gene was found in a subtelomere, the gene was removed along with the 10 kb surrounding it on each side. Gene deserts were defined as regions of greater than 1 Mb between two adjacent genes, with the 10 kb proximal to each gene removed. From all three types of regions, any known Pol II binding sites[17] or DNase I hypersensitive sites [25] with 100 bp flanking regions were removed in order to exclude regions that may be related to the adjacent genes.


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)

A diagram outlining the analysis that was performed on the data. The diagram uses the example of gene deserts to describe the analysis, but the same techniques were used for pericentromeres, subtelomeres and silent, medium expression and high expression genes.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: A diagram outlining the analysis that was performed on the data. The diagram uses the example of gene deserts to describe the analysis, but the same techniques were used for pericentromeres, subtelomeres and silent, medium expression and high expression genes.
Mentions: To characterize the histone modifications that are enriched in different regions of the genome, we first obtained the locations of each type of region. Our determinations were made based upon gene annotations (see Methods and Figure 1 for details). Pericentromeres were defined for each chromosome as the region between the two genes most proximal to the centromeric gap in the genome assembly. From this region, the 10 kb nearest to each of the genes was removed since it could contain regulatory elements for the genes. Subtelomeres designations from [24] were used as a starting point. If a gene was found in a subtelomere, the gene was removed along with the 10 kb surrounding it on each side. Gene deserts were defined as regions of greater than 1 Mb between two adjacent genes, with the 10 kb proximal to each gene removed. From all three types of regions, any known Pol II binding sites[17] or DNase I hypersensitive sites [25] with 100 bp flanking regions were removed in order to exclude regions that may be related to the adjacent genes.

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