A large fraction of extragenic RNA pol II transcription sites overlap enhancers.
Francesca De Santa,Iros Barozzi,Flore Mietton,Serena Ghisletti,Sara Polletti,Betsabeh Khoramian Tusi,Heiko Muller,Jiannis Ragoussis,Chia-Lin Wei,Gioacchino Natoli +9 more
TLDR
A substantial fraction of extragenic Pol II transcription sites coincides with transcriptional enhancers, which may be relevant for functional annotation of mammalian genomes.Abstract:
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.read more
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The M1 and M2 paradigm of macrophage activation: time for reassessment.
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Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses
Moran N. Cabili,Cole Trapnell,Cole Trapnell,Loyal A. Goff,Magdalena J. Koziol,Magdalena J. Koziol,Barbara Tazon-Vega,Barbara Tazon-Vega,Aviv Regev,John L. Rinn,John L. Rinn +10 more
TL;DR: It is found that lincRNA expression is strikingly tissue-specific compared with coding genes, and that l incRNAs are typically coexpressed with their neighboring genes, albeit to an extent similar to that of pairs of neighboring protein-coding genes.
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Genome Regulation by Long Noncoding RNAs
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TL;DR: Long noncoding RNAs (lncRNAs) as discussed by the authors form extensive networks of ribonucleoprotein (RNP) complexes with numerous chromatin regulators and then target these enzymatic activities to appropriate locations in the genome.
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Mapping and analysis of chromatin state dynamics in nine human cell types
Jason Ernst,Pouya Kheradpour,Pouya Kheradpour,Tarjei S. Mikkelsen,Noam Shoresh,Lucas D. Ward,Lucas D. Ward,Charles B. Epstein,Xiaolan Zhang,Li Wang,Robbyn Issner,Michael Coyne,Manching Ku,Manching Ku,Manching Ku,Timothy Durham,Manolis Kellis,Manolis Kellis,Bradley E. Bernstein,Bradley E. Bernstein,Bradley E. Bernstein +20 more
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Unique features of long non-coding RNA biogenesis and function
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TL;DR: This Review describes special events in the lifetimes of lncRNAs — before, during and after transcription — and discusses how these events ultimately shape the unique characteristics and functional roles of lNCRNAs.
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TL;DR: Functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project are reported, providing convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts.
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TL;DR: The rapidly advancing field of long ncRNAs is reviewed, describing their conservation, their organization in the genome and their roles in gene regulation, and the medical implications.
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Evolution and functions of long noncoding RNAs
TL;DR: The evolution of long noncoding RNAs and their roles in transcriptional regulation, epigenetic gene regulation, and disease are reviewed.
Journal ArticleDOI
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