RRC ID 38214
著者 Kratz A, Arner E, Saito R, Kubosaki A, Kawai J, Suzuki H, Carninci P, Arakawa T, Tomita M, Hayashizaki Y, Daub CO.
タイトル Core promoter structure and genomic context reflect histone 3 lysine 9 acetylation patterns.
ジャーナル BMC Genomics
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.
巻・号 11
ページ 257
公開日 2010-4-21
DOI 10.1186/1471-2164-11-257
PII 1471-2164-11-257
PMID 20409305
PMC PMC2867832
MeSH Acetylation Cell Line Chromatin Immunoprecipitation Gene Expression Regulation Genome, Human* Histone Code* Histones / metabolism Humans Lysine / metabolism Promoter Regions, Genetic* RNA Polymerase II / metabolism
IF 3.594
引用数 21
WOS 分野 BIOTECHNOLOGY & APPLIED MICROBIOLOGY GENETICS & HEREDITY
リソース情報
ヒト・動物細胞