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Nascent RNA Sequencing Reveals Widespread Pausing and Divergent Initiation at Human Promoters
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Nascent RNA Sequencing Reveals Widespread Pausing and Divergent Initiation at Human Promoters
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Journal Article
Nascent RNA Sequencing Reveals Widespread Pausing and Divergent Initiation at Human Promoters
2008
Overview
RNA polymerases are highly regulated molecular machines. We present a method (global run-on sequencing, GRO-seq) that maps the position, amount, and orientation of transcriptionally engaged RNA polymerases genome-wide. In this method, nuclear run-on RNA molecules are subjected to large-scale parallel sequencing and mapped to the genome. We show that peaks of promoter-proximal polymerase reside on ~30% of human genes, transcription extends beyond pre-messenger RNA 3' cleavage, and antisense transcription is prevalent. Additionally, most promoters have an engaged polymerase upstream and in an orientation opposite to the annotated gene. This divergent polymerase is associated with active genes but does not elongate effectively beyond the promoter. These results imply that the interplay between polymerases and regulators over broad promoter regions dictates the orientation and efficiency of productive transcription.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
Biological and medical sciences
/ DNA-Directed RNA Polymerases - metabolism
/ Fundamental and applied biological sciences. Psychology
/ Genes
/ Genomes
/ Genomics
/ Histones
/ Humans
/ Molecular and cellular biology
/ RNA
/ RNA Polymerase II - metabolism
/ Transcription Initiation Site
/ Transcription. Transcription factor. Splicing. Rna processing
