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A multiplicity of factors contributes to selective RNA polymerase III occupancy of a subset of RNA polymerase III genes in mouse liver

    • 1Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland;
    • 2Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland;
    • 3Department of Molecular Biology, Faculty of Sciences, University of Geneva, 1211 Geneva, Switzerland;
    • 4Département de formation et de recherche, Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1011 Lausanne, Switzerland
    • 9Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland.
    • 10Swiss Institute of Bioinformatics, University of Lausanne, Lausanne, Switzerland.
    • 11Interfaculty Institute of Bioengineering, School of Life Sciences, Ecole polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
    • 12Vital IT, Swiss Institute of Bioinformatics, Lausanne, Switzerland.
    • 13Bioinformatics and Biostatistics Core Facility, School of Life Sciences, Ecole polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
    • 14Department of Molecular Biology, Faculty of Sciences, University of Geneva, Lausanne, Switzerland.
    • 15Département de formation et de recherche, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
    • 5 These authors contributed equally to this work.
    • 6 These authors contributed equally to this work.
    • 7 A complete list of consortium authors appears at the end of this manuscript.
    • 8 Corresponding authors. E-mail [email protected]. E-mail [email protected].
Published January 27, 2012. https://doi.org/10.1101/gr.130286.111
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Abstract

The genomic loci occupied by RNA polymerase (RNAP) III have been characterized in human culture cells by genome-wide chromatin immunoprecipitations, followed by deep sequencing (ChIP-seq). These studies have shown that only ∼40% of the annotated 622 human tRNA genes and pseudogenes are occupied by RNAP-III, and that these genes are often in open chromatin regions rich in active RNAP-II transcription units. We have used ChIP-seq to characterize RNAP-III-occupied loci in a differentiated tissue, the mouse liver. Our studies define the mouse liver RNAP-III-occupied loci including a conserved mammalian interspersed repeat (MIR) as a potential regulator of an RNAP-III subunit-encoding gene. They reveal that synteny relationships can be established between a number of human and mouse RNAP-III genes, and that the expression levels of these genes are significantly linked. They establish that variations within the A and B promoter boxes, as well as the strength of the terminator sequence, can strongly affect RNAP-III occupancy of tRNA genes. They reveal correlations with various genomic features that explain the observed variation of 81% of tRNA scores. In mouse liver, loci represented in the NCBI37/mm9 genome assembly that are clearly occupied by RNAP-III comprise 50 Rn5s (5S RNA) genes, 14 known non-tRNA RNAP-III genes, nine Rn4.5s (4.5S RNA) genes, and 29 SINEs. Moreover, out of the 433 annotated tRNA genes, half are occupied by RNAP-III. Transfer RNA gene expression levels reflect both an underlying genomic organization conserved in dividing human culture cells and resting mouse liver cells, and the particular promoter and terminator strengths of individual genes.

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