TY - JOUR
T1 - Determination of enriched histone modifications in non-genic portions of the human genome
AU - Rosenfeld, Jeffrey A.
AU - Wang, Zhibin
AU - Schones, Dustin E.
AU - Zhao, Keji
AU - DeSalle, Rob
AU - Zhang, Michael Q.
N1 - Funding Information:
We thank Dan Tranchina, Andrew Smith, Zhenyu Xuan, Xiaoyue Zhao, and Rob Martienssen for helpful discussions. We would also like to thank Steve Small, Ken Birnbaum, Christopher Vakoc, and Matt Vaughn who read and commented on the manuscript. We would also like to thank Todd Hey-wood of the Cold Spring Harbor High Performance Computing Center who provided assistance in making sure that adequate computational facilities were available for this study. This work was partially supported by NIH grant HG10696 to M.Q.Z. and by the Intramural Research Program of the NIH National Heart, Lung, and Blood Institute (ZW, DES, KZ). J.A.R is supported by an NIH training grant to New York University and is further supported by a McCracken Fellowship. We would also like to thank the three anonymous reviewers for their helpful comments.
PY - 2009/3/31
Y1 - 2009/3/31
N2 - 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.
AB - 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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U2 - 10.1186/1471-2164-10-143
DO - 10.1186/1471-2164-10-143
M3 - Article
C2 - 19335899
AN - SCOPUS:64849110610
SN - 1471-2164
VL - 10
JO - BMC genomics
JF - BMC genomics
M1 - 143
ER -