Evidence map›Paper›PMID 27259512›Full record

ArticleGenome biology2016

Comprehensive analysis of promoter-proximal RNA polymerase II pausing across mammalian cell types.

Daniel S Day, Bing Zhang, Sean M Stevens, Francesco Ferrari, Erica N Larschan, Peter J Park, William T Pu

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
3.8field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

74 citing papers in PubMed, 109 citations in OpenAlex.

  1. Article
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  7. Small RNA Analysis in Cancer Cells.Methods in molecular biology (Clifton, N.J.) · 2026
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14 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 1 country.

Daniel S DayDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, 02115, USA.
Bing ZhangDepartment of Cardiology, Boston Children's Hospital, Boston, MA, 02115, USA. bingzhang@sjtu.edu.cn.
Sean M StevensDepartment of Cardiology, Boston Children's Hospital, Boston, MA, 02115, USA.
Francesco FerrariDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, 02115, USA.
Erica N LarschanDepartment of Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, RI, 02912, USA.
Peter J ParkDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, 02115, USA. peter_park@hms.harvard.edu.
William T PuDepartment of Cardiology, Boston Children's Hospital, Boston, MA, 02115, USA. wpu@pulab.org.
Boston Children's Hospital · USHarvard University · USBrown University · USHarvard–MIT Division of Health Sciences and Technology · US

Funding

RESEARCH METHODS IN PEDIATRICS HEART DISEASET32HL007572 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI Sarah D DE FERRANTI, Jane W. Newburger · 1985 to 2026
$13.0M
Mapping Transcriptional Networks in Cardiac DevelopmentU01HL098166 · NHLBI · HARVARD MEDICAL SCHOOL · PI SEIDMAN, JONATHAN G · 2009 to 2014
$9.5M
Regulation of Cardiac Development in Health and DiseaseUM1HL098166 · NHLBI · HARVARD MEDICAL SCHOOL · PI PENNACCHIO, LEN ALEXANDER, PU, WILLIAM TSWENCHING · 2015 to 2019
$4.4M
Establishing coordinate gene regulation during Drosophila dosage compensationR01GM098461 · NIGMS · BROWN UNIVERSITY · PI LARSCHAN, ERICA NICOLE · 2011 to 2016
$2.1M
NHLBI NIH HHS T32 HL007572NHLBI NIH HHS U01 HL098166NHLBI NIH HHS UM1 HL098166NIGMS NIH HHS R01 GM098461
6 · The paper itself

Abstract

backgroundFor many genes, RNA polymerase II stably pauses before transitioning to productive elongation. Although polymerase II pausing has been shown to be a mechanism for regulating transcriptional activation, the extent to which it is involved in control of mammalian gene expression and its relationship to chromatin structure remain poorly understood.

resultsHere, we analyze 85 RNA polymerase II chromatin immunoprecipitation (ChIP)-sequencing experiments from 35 different murine and human samples, as well as related genome-wide datasets, to gain new insights into the relationship between polymerase II pausing and gene regulation. Across cell and tissue types, paused genes (pausing index > 2) comprise approximately 60 % of expressed genes and are repeatedly associated with specific biological functions. Paused genes also have lower cell-to-cell expression variability. Increased pausing has a non-linear effect on gene expression levels, with moderately paused genes being expressed more highly than other paused genes. The highest gene expression levels are often achieved through a novel pause-release mechanism driven by high polymerase II initiation. In three datasets examining the impact of extracellular signals, genes responsive to stimulus have slightly lower pausing index on average than non-responsive genes, and rapid gene activation is linked to conditional pause-release. Both chromatin structure and local sequence composition near the transcription start site influence pausing, with divergent features between mammals and Drosophila. Most notably, in mammals pausing is positively correlated with histone H2A.Z occupancy at promoters.

conclusionsOur results provide new insights into the contribution of RNA polymerase II pausing in mammalian gene regulation and chromatin structure.

Indexed as

Promoter Regions, GeneticTranscription, GeneticAnimalsCell LineageChromatinDrosophila melanogasterGene Expression RegulationGenome, HumanHistonesHumansMiceRNA Polymerase IIChromatinhistone H2A.F-ZHistonesRNA Polymerase II

Identifiers

PMID27259512
PMCPMC4893286
OpenAlexW2417661205

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.