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Open Access Highly Accessed Research article

Evidence for sequence biases associated with patterns of histone methylation

Zhong Wang12 and Huntington F Willard1*

Author affiliations

1 Genome Biology Group, Duke Institute for Genome Sciences & Policy, Duke University, 101 Science Dr. CIEMAS 2376, Durham, NC, 27708, USA

2 DOE Joint Genome Institute, Walnut Creek, CA, 94598, USA

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Citation and License

BMC Genomics 2012, 13:367  doi:10.1186/1471-2164-13-367

Published: 2 August 2012



Combinations of histone variants and modifications, conceptually representing a histone code, have been proposed to play a significant role in gene regulation and developmental processes in complex organisms. While various mechanisms have been implicated in establishing and maintaining epigenetic patterns at specific locations in the genome, they are generally believed to be independent of primary DNA sequence on a more global scale.


To address this systematically in the case of the human genome, we have analyzed primary DNA sequences underlying patterns of 19 different methylated histones in human primary T-cells and patterns of three methylated histones across additional human cell lines. We report strong sequence biases associated with most of these histone marks genome-wide in each cell type. Furthermore, the sequence characteristics for such association are distinct for different groups of histone marks.


These findings provide evidence of an influence of genomic sequence on patterns of histone modification associated with gene expression and chromatin programming, and they suggest that the mechanisms responsible for global histone modifications may interpret genomic sequence in various ways.