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Nucleosome rotational setting is associated with transcriptional regulation in promoters of tissue-specific human genes.

ABSTRACT: BACKGROUND: The position of a nucleosome, both translational along the DNA molecule and rotational between the histone core and the DNA, is controlled by many factors, including the regular occurrence of specific dinucleotides with a period of approximately 10 bp, important for the rotational setting of the DNA around the histone octamer. RESULTS: We show that such a 10 bp periodic signal of purine-purine dinucleotides occurs in phase with the transcription start site (TSS) of human genes and is centered on the position of the first (+1) nucleosome downstream of the TSS. These data support a direct link between transcription and the rotational setting of the nucleosome. The periodic signal is most prevalent in genes that contain CpG islands that are expressed at low levels in a tissue-specific manner and are involved in the control of transcription. CONCLUSIONS: These results, together with several lines of evidence from the recent literature, support a new model whereby the +1 nucleosome could be more efficiently disassembled from gene promoters by H3K56 acetylation marks if the periodic signal specifies an optimal rotational setting.

SUBMITTER: Hebert C

PROVIDER: S-EPMC2898081 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Nucleosome rotational setting is associated with transcriptional regulation in promoters of tissue-specific human genes.

Hebert Charles C Roest Crollius Hugues H

Genome biology 20100512 5

<h4>Background</h4>The position of a nucleosome, both translational along the DNA molecule and rotational between the histone core and the DNA, is controlled by many factors, including the regular occurrence of specific dinucleotides with a period of approximately 10 bp, important for the rotational setting of the DNA around the histone octamer.<h4>Results</h4>We show that such a 10 bp periodic signal of purine-purine dinucleotides occurs in phase with the transcription start site (TSS) of human ...[more]

PMID: 20462404

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Project description:Transcriptome diversity provides the key to cellular identity. One important contribution to expression diversity is the use of alternative promoters, which creates mRNA isoforms by expanding the choice of transcription initiation sites of a gene. The proximity of the basal promoter to the transcription initiation site enables prediction of a promoter's location based on the gene annotations. We show that annotation of alternative promoters regulating expression of transcripts with distinct first exons enables a novel methodology to quantify expression levels and tissue specificity of mRNA isoforms.The use of distinct alternative first exons in 3,296 genes was examined using exon-microarray data from 11 human tissues. Comparing two transcripts from each gene we found that the activity of alternative promoters (i.e., P1 and P2) was not correlated through tissue specificity or level of expression. Furthermore neither P1 nor P2 conferred any bias for tissue-specific or ubiquitous expression. Genes associated with specific diseases produced transcripts whose limited expression patterns were consistent with the tissue affected in disease. Notably, genes that were historically designated as tissue-specific or housekeeping had alternative isoforms that showed differential expression. Furthermore, only a small number of alternative promoters showed expression exclusive to a single tissue indicating that "tissue preference" provides a better description of promoter activity than tissue specificity. When compared to gene expression data in public databases, as few as 22% of the genes had detailed information for more than one isoform, whereas the remainder collapsed the expression patterns from individual transcripts into one profile.We describe a computational pipeline that uses microarray data to assess the level of expression and breadth of tissue profiles for transcripts with distinct first exons regulated by alternative promoters. We conclude that alternative promoters provide individualized regulation that is confirmed through expression levels, tissue preference and chromatin modifications. Although the selective use of alternative promoters often goes uncharacterized in gene expression analyses, transcripts produced in this manner make unique contributions to the cell that requires further exploration.

Dataset Information

Nucleosome rotational setting is associated with transcriptional regulation in promoters of tissue-specific human genes.

Publications

Nucleosome rotational setting is associated with transcriptional regulation in promoters of tissue-specific human genes.

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