Discovery and annotation of functional chromatin signatures in the human genome.
|Title||Discovery and annotation of functional chromatin signatures in the human genome.|
|Publication Type||Journal Article|
|Year of Publication||2009|
|Authors||Hon G, Wang W, Ren B|
|Journal||PLoS Comput Biol|
|Date Published||2009 Nov|
|Keywords||Algorithms, Alternative Splicing, Chromatin, Exons, Gene Expression Regulation, Genome, Human, Humans, Models, Genetic, Normal Distribution, Nucleosomes, Regulatory Elements, Transcriptional, Regulatory Sequences, Nucleic Acid, Statistics, Nonparametric|
Transcriptional regulation in human cells is a complex process involving a multitude of regulatory elements encoded by the genome. Recent studies have shown that distinct chromatin signatures mark a variety of functional genomic elements and that subtle variations of these signatures mark elements with different functions. To identify novel chromatin signatures in the human genome, we apply a de novo pattern-finding algorithm to genome-wide maps of histone modifications. We recover previously known chromatin signatures associated with promoters and enhancers. We also observe several chromatin signatures with strong enrichment of H3K36me3 marking exons. Closer examination reveals that H3K36me3 is found on well-positioned nucleosomes at exon 5' ends, and that this modification is a global mark of exon expression that also correlates with alternative splicing. Additionally, we observe strong enrichment of H2BK5me1 and H4K20me1 at highly expressed exons near the 5' end, in contrast to the opposite distribution of H3K36me3-marked exons. Finally, we also recover frequently occurring chromatin signatures displaying enrichment of repressive histone modifications. These signatures mark distinct repeat sequences and are associated with distinct modes of gene repression. Together, these results highlight the rich information embedded in the human epigenome and underscore its value in studying gene regulation.
|Alternate Journal||PLoS Comput. Biol.|