Tight associations between transcription promoter type and epigenetic variation in histone positioning and modification
1 Institute for Advanced Biosciences, Keio University, Tsuruoka, 997-0017, Japan
2 Systems Biology Program, Department of Environment and Information Studies, Keio University, Fujisawa, 252-8520, Japan
3 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02445, USA
4 Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, 252-8520, Japan
5 Systems Biology Program, Department of Environment and Information Studies, Keio University, Fujisawa, Kanagawa 252-8520, Japan
6 Donnelly Centre of Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S-3E1, Canada
7 Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
8 Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045 Japan
BMC Genomics 2011, 12:416 doi:10.1186/1471-2164-12-416Published: 17 August 2011
Transcription promoters are fundamental genomic cis-elements controlling gene expression. They can be classified into two types by the degree of imprecision of their transcription start sites: peak promoters, which initiate transcription from a narrow genomic region; and broad promoters, which initiate transcription from a wide-ranging region. Eukaryotic transcription initiation is suggested to be associated with the genomic positions and modifications of nucleosomes. For instance, it has been recently shown that histone with H3K9 acetylation (H3K9ac) is more likely to be distributed around broad promoters rather than peak promoters; it can thus be inferred that there is an association between histone H3K9 and promoter architecture.
Here, we performed a systematic analysis of transcription promoters and gene expression, as well as of epigenetic histone behaviors, including genomic position, stability within the chromatin, and several modifications. We found that, in humans, broad promoters, but not peak promoters, generally had significant associations with nucleosome positioning and modification. Specifically, around broad promoters histones were highly distributed and aligned in an orderly fashion. This feature was more evident with histones that were methylated or acetylated; moreover, the nucleosome positions around the broad promoters were more stable than those around the peak ones. More strikingly, the overall expression levels of genes associated with broad promoters (but not peak promoters) with modified histones were significantly higher than the levels of genes associated with broad promoters with unmodified histones.
These results shed light on how epigenetic regulatory networks of histone modifications are associated with promoter architecture.