Research article

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

Jeffrey A Rosenfeld^1,2,3 , Zhibin Wang⁴ , Dustin E Schones⁴ , Keji Zhao⁴ , Rob DeSalle³ and Michael Q Zhang¹

¹Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724 USA

²Department of Biology, New York University, New York, NY USA

³American Museum of Natural History, New York, NY USA

⁴Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, NIH, Bethesda, MD USA

author email corresponding author email

BMC Genomics 2009, 10:143doi:10.1186/1471-2164-10-143

Published:	31 March 2009

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.