title: Core promoter structure and genomic context reflect histone 3 lysine 9 acetylation patterns.
abstract: BACKGROUND
  Histone modifications play an important role in gene regulation. Acetylation of histone 3 lysine 9 (H3K9ac) is generally associated with transcription initiation and unfolded chromatin, thereby positively influencing gene expression. Deep sequencing of the 5' ends of gene transcripts using DeepCAGE delivers detailed information about the architecture and expression level of gene promoters. The combination of H3K9ac ChIP-chip and DeepCAGE in a myeloid leukemia cell line (THP-1) allowed us to study the spatial distribution of H3K9ac around promoters using a novel clustering approach. The promoter classes were analyzed for association with relevant genomic sequence features.
  
  
  RESULTS
  We performed a clustering of 4,481 promoters according to their surrounding H3K9ac signal and analyzed the clustered promoters for association with different sequence features. The clustering revealed three groups with major H3K9ac signal upstream, centered and downstream of the promoter. Narrow single peak promoters tend to have a concentrated activity of H3K9ac in the upstream region, while broad promoters tend to have a concentrated activity of H3K9ac and RNA polymerase II binding in the centered and downstream regions. A subset of promoters with high gene expression level, compared to subsets with low and medium gene expression, shows dramatic increase in H3K9ac activity in the upstream cluster only; this may indicate that promoters in the centered and downstream clusters are predominantly regulated at post-initiation steps. Furthermore, the upstream cluster is depleted in CpG islands and more likely to regulate un-annotated genes.
  
  
  CONCLUSIONS
  Clustering core promoters according to their surrounding acetylation signal is a promising approach for the study of histone modifications. When examining promoters clustered into groups according to their surrounding H3K9 acetylation signal, we find that the relative localization and intensity of H3K9ac is very specific depending on characteristic sequence features of the promoter. Experimental data from DeepCAGE and ChIP-chip experiments using undifferentiated (monocyte) and differentiated (macrophage) THP-1 cells leads us to the same conclusions.
authors.affiliation: Keiko University, Graduate School of Media and Governance, Kanagawa, Japan.
authors.forename: Anton
authors.initials: A
authors.lastname: Kratz
authors.forename: Erik
authors.initials: E
authors.lastname: Arner
authors.forename: Rintaro
authors.initials: R
authors.lastname: Saito
authors.forename: Atsutaka
authors.initials: A
authors.lastname: Kubosaki
authors.forename: Jun
authors.initials: J
authors.lastname: Kawai
authors.forename: Harukazu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Piero
authors.initials: P
authors.lastname: Carninci
authors.forename: Takahiro
authors.initials: T
authors.lastname: Arakawa
authors.forename: Masaru
authors.initials: M
authors.lastname: Tomita
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: Carsten O
authors.initials: CO
authors.lastname: Daub
mesh_terms: D000107:Acetylation; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation; D015894:Genome, Human; D042421:Histone Code; D006657:Histones / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism
chemical_list: D006657:Histones; D012319:RNA Polymerase II; D008239:Lysine
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