Dataset Information

Alternative polyadenylation sites reveal distinct chromatin accessibility and histone modification in human cell lines.

ABSTRACT: MOTIVATION:In addition to alternative splicing, alternative polyadenylation has also been identified as a critical and prevalent regulatory mechanism in human gene expression. However, the mechanism of alternative polyadenylation selection and the involved factors is still largely unknown. RESULTS:We use the ENCODE data to scan DNA functional elements, including chromatin accessibility and histone modification, around transcript cleavage sites. Our results demonstrate that polyadenylation sites tend to be less sensitive to DNase I. However, these polyadenylation sites have preference in nucleosome-depleted regions, indicating the involvement of chromatin higher-order structure rather than nucleosomes in the resultant lower chromatin accessibility. More interestingly, for genes using two polyadenylation sites, the distal sites show even lower chromatin accessibility compared with the proximal sites or the unique sites of genes using only one polyadenylation site. We also observe that the histone modification mark, histone H3 lysine 36 tri-methylation (H3K36Me3), exhibits different patterns around the cleavage sites of genes using multiple polyadenylation sites from those of genes using a single polyadenylation site. Surprisingly, the H3K36Me3 levels are comparable among the alternative polyadenylation sites themselves. In summary, polyadenylation and alternative polyadenylation are closely related to functional elements on the DNA level. CONTACT:liang.chen@usc.edu.

SUBMITTER: Lee CY

PROVIDER: S-EPMC3702257 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Alternative polyadenylation sites reveal distinct chromatin accessibility and histone modification in human cell lines.

Lee Che-yu CY Chen Liang L

Bioinformatics (Oxford, England) 20130605 14

<h4>Motivation</h4>In addition to alternative splicing, alternative polyadenylation has also been identified as a critical and prevalent regulatory mechanism in human gene expression. However, the mechanism of alternative polyadenylation selection and the involved factors is still largely unknown.<h4>Results</h4>We use the ENCODE data to scan DNA functional elements, including chromatin accessibility and histone modification, around transcript cleavage sites. Our results demonstrate that polyade ...[more]

PMID: 23740743

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Project description:Histone modification has emerged as a very important mechanism regulating the transcriptional status of the genome. Insulin-like growth factor 2 (IGF2) is a peptide hormone controlling various cellular processes, including proliferation and apoptosis. H19 gene is closely linked to IGF2 gene, and IGF2 and H19 are reciprocally regulated imprinted genes. The epigenetic signature of H19 promoter (hypermethylation) on the paternal allele plays a vital role in allowing the expression of the paternal allele of IGF2.46 Our previous studies demonstrate that butyrate regulates the expression of IGF2 as well as genes encoding IGF Binding proteins. To obtain further understanding of histone modification and its regulatory potentials in controlling IGF2/H19 gene expression, we investigated the histone modification status of some key histones associated with the expression of IGF2/H19 genes in bovine cells using RNA-seq in combination with Chip-seq technology. A high-resolution map of the major chromatin modification at the IGF2/H19 locus induced by butyrate was constructed to illustrate the fundamental association of the chromatin modification landscape that may play a role in the activation of the IGF2 gene. High-definition epigenomic landscape mapping revealed that IGF2 and H19 have distinct chromatin modification patterns at their coding and promoter regions, such as TSSs and TTSs. Moreover, the correlation between the differentially methylated regions (DMRs) of IGF2/H19 locus and histone modification (acetylation and methylation) indicated that epigenetic signatures/markers of DNA methylation, histone methylation and histone acetylation were differentially distributed on the expressed IGF2 and silenced H19 genes. Our evidence also suggests that butyrate-induced regional changes of histone acetylation statusin the upstream regulation domain of H19 may be related to the reduced expression of H19 and strong activation of IGF2. Our results provided insights into the mechanism of butyrate-induced loss of imprinting (LOI) of IGF2 and regulation of gene expression by histone modification.

Dataset Information

Alternative polyadenylation sites reveal distinct chromatin accessibility and histone modification in human cell lines.

Publications

Alternative polyadenylation sites reveal distinct chromatin accessibility and histone modification in human cell lines.

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