Evidence map›Paper›PMID 24972996›Full record

ArticleGenome biology2014

Characteristic bimodal profiles of RNA polymerase II at thousands of active mammalian promoters.

Mathieu Quinodoz, Cédric Gobet, Felix Naef, Kyle B Gustafson

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Article in Genome biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

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23citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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3 · Its place in the literature

Who cites it

23 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Mathieu Quinodoz
Cédric Gobet
Felix Naef
Kyle B Gustafson

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIn mammals, ChIP-seq studies of RNA polymerase II (PolII) occupancy have been performed to reveal how recruitment, initiation and pausing of PolII may control transcription rates, but the focus is rarely on obtaining finely resolved profiles that can portray the progression of PolII through sequential promoter states.

resultsHere, we analyze PolII binding profiles from high-coverage ChIP-seq on promoters of actively transcribed genes in mouse and humans. We show that the enrichment of PolII near transcription start sites exhibits a stereotypical bimodal structure, with one peak near active transcription start sites and a second peak 110 base pairs downstream from the first. Using an empirical model that reliably quantifies the spatial PolII signal, gene by gene, we show that the first PolII peak allows for refined positioning of transcription start sites, which is corroborated by mRNA sequencing. This bimodal signature is found both in mouse and humans. Analysis of the pausing-related factors NELF and DSIF suggests that the downstream peak reflects widespread pausing at the +1 nucleosome barrier. Several features of the bimodal pattern are correlated with sequence features such as CpG content and TATA boxes, as well as the histone mark H3K4me3.

conclusionsWe thus show how high coverage DNA sequencing experiments can reveal as-yet unnoticed bimodal spatial features of PolII accumulation that are frequent at individual mammalian genes and reminiscent of transcription initiation and pausing. The initiation-pausing hypothesis is corroborated by evidence from run-on sequencing and immunoprecipitation in other cell types and species.

Indexed as

Promoter Regions, GeneticAnimalsChromatin ImmunoprecipitationHeLa CellsHistonesHumansMiceProtein BindingRNA, MessengerRNA Polymerase IITranscription, GeneticTranscription Initiation SiteHistonesRNA, MessengerRNA Polymerase II

Identifiers

PMID24972996
PMCPMC4197824

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.