A Large Fraction of Extragenic RNA Pol II Transcription Sites Overlap Enhancers

Mammalian genomes are pervasively transcribed outside mapped protein-coding genes. One class of extragenic transcription products is represented by long non-coding RNAs (lncRNAs), some of which result from Pol_II transcription of bona-fide RNA genes. Whether all lncRNAs described insofar are product...

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Published in:PLoS biology Vol. 8; no. 5; p. e1000384
Main Authors: De Santa, Francesca, Barozzi, Iros, Mietton, Flore, Ghisletti, Serena, Polletti, Sara, Tusi, Betsabeh Khoramian, Muller, Heiko, Ragoussis, Jiannis, Wei, Chia-Lin, Natoli, Gioacchino
Format: Journal Article
Language:English
Published: United States Public Library of Science 01.05.2010
Public Library of Science (PLoS)
Subjects:
Animals
Binding Sites
Binding sites (Biochemistry)
Cell Biology/Gene Expression
Cell Biology/Leukocyte Signaling and Gene Expression
Experiments
Female
Fractions
Gene Expression Regulation
Genetic transcription
Genetics
Genetics and Genomics/Epigenetics
Genomes
Genomics
Humans
Immunology/Innate Immunity
Lipopolysaccharides - immunology
Macrophage Activation - immunology
Mice
Molecular Biology/Histone Modification
Noise
Physiological aspects
Promoter Regions, Genetic - genetics
Proteins
Regulatory Sequences, Nucleic Acid
RNA polymerase
RNA Polymerase II - genetics
RNA Polymerase II - metabolism
RNA polymerases
RNA, Untranslated - genetics
Signatures
Transcription, Genetic
Italy
United Kingdom
Singapore
Promoter Regions, Genetic
Humans
RNA, Untranslated
Regulatory Sequences, Nucleic Acid
Gene Expression Regulation
Lipopolysaccharides
Macrophage Activation
Animals
Female
Transcription, Genetic
Mice
Binding Sites
RNA Polymerase II
ISSN:1545-7885, 1544-9173, 1545-7885
Online Access:Get full text
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Summary:Mammalian genomes are pervasively transcribed outside mapped protein-coding genes. One class of extragenic transcription products is represented by long non-coding RNAs (lncRNAs), some of which result from Pol_II transcription of bona-fide RNA genes. Whether all lncRNAs described insofar are products of RNA genes, however, is still unclear. Here we have characterized transcription sites located outside protein-coding genes in a highly regulated response, macrophage activation by endotoxin. Using chromatin signatures, we could unambiguously classify extragenic Pol_II binding sites as belonging to either canonical RNA genes or transcribed enhancers. Unexpectedly, 70% of extragenic Pol_II peaks were associated with genomic regions with a canonical chromatin signature of enhancers. Enhancer-associated extragenic transcription was frequently adjacent to inducible inflammatory genes, was regulated in response to endotoxin stimulation, and generated very low abundance transcripts. Moreover, transcribed enhancers were under purifying selection and contained binding sites for inflammatory transcription factors, thus suggesting their functionality. These data demonstrate that a large fraction of extragenic Pol_II transcription sites can be ascribed to cis-regulatory genomic regions. Discrimination between lncRNAs generated by canonical RNA genes and products of transcribed enhancers will provide a framework for experimental approaches to lncRNAs and help complete the annotation of mammalian genomes.
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The author(s) have made the following declarations about their contributions: Conceived and designed the experiments: FDS IB GN. Performed the experiments: FDS FM SG SP BKT. Analyzed the data: FDS IB FM SG SP HM GN. Contributed reagents/materials/analysis tools: JR CLW. Wrote the paper: GN.
ISSN:1545-7885
1544-9173
1545-7885
DOI:10.1371/journal.pbio.1000384