Abstract
Author SummaryMammalian genomes contain vast intergenic regions that are extensively transcribed and generate various types of short and long non-coding RNAs (ncRNAs). Although in some cases specific functions have been assigned to intergenic transcripts, the functional significance of this transcriptional output remains largely unknown, and the possibility exists that part of this transcription reflects noise generated by random collisions of the transcriptional machinery with the genome to generate meaningless transcription. In this study we used chromatin signatures to characterize extragenic transcription sites targeted by RNA Polymerase II (RNA Pol II) in a highly regulated response—endotoxin activation of macrophages. We found that a significant portion of extragenic transcription sites are associated with the chromatin signature characteristic of enhancers. Consistent with their chromatin signature, we found that these extragenic transcription sites are under purifying selection and contain binding sites for inflammatory transcription factors, as well as for PU.1, a hematopoietic transcription factor that marks enhancers in macrophages. Moreover, much of this extragenic transcription is regulated by stimulation. We also identified hundreds of transcribed regions with a signature of canonical RNA genes. Our data indicate that extragenic transcription sites can be efficiently classified using chromatin signatures, which will be relevant for functional annotation of mammalian genomes.
Highlights
A most striking finding of modern genomic biology has been the identification of a large amount of transcription that occurs outside mapped protein-coding genes and generates a heterogeneous spectrum of transcripts [1,2], which may in principle exert broad regulatory or effector functions [3,4,5]
In this study we used chromatin signatures to characterize extragenic transcription sites targeted by RNA Polymerase II (RNA Pol II) in a highly regulated response—endotoxin activation of macrophages
We found that a significant portion of extragenic transcription sites are associated with the chromatin signature characteristic of enhancers
Summary
A most striking finding of modern genomic biology has been the identification of a large amount of transcription that occurs outside mapped protein-coding genes and generates a heterogeneous spectrum of transcripts [1,2], which may in principle exert broad regulatory or effector functions [3,4,5]. These data imply that the amount of information contained in the complex genomes of eukaryotes, and higher eukaryotes in particular, is much higher than the classical linear models of genomic organization can accommodate [6]. Evidence for functionality of lncRNAs as a class stems from evolutionary analyses indicating that purifying selection has acted on both the promoters and the internal sequences of lncRNA genes to eliminate nucleotide substitutions, insertions and deletions [3,8,24,25]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
