Evidence map›Paper›PMID 24655370›Full record

ArticleGenome biology2014

Genomic occupancy of Runx2 with global expression profiling identifies a novel dimension to control of osteoblastogenesis.

Hai Wu, Troy W Whitfield, Jonathan A R Gordon, Jason R Dobson, Phillip W L Tai, Andre J van Wijnen, Janet L Stein, Gary S Stein, Jane B Lian

Open access · goldAbstract read
In one paragraph

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 102 papers.

0numbers the graph read from it
0cells of the map it votes in
102citing papers in PubMed
7.3field-weighted citation impact, top 2% 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

102 citing papers in PubMed, 146 citations in OpenAlex.

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  13. Downregulation of Nesprin1 by Runx2 deficiency is critical for the development of skeletal laminopathy-like pathology.Proceedings of the National Academy of Sciences of the United States of America · 2025
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42 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

9 authors at 4 institutions in 1 country.

Hai Wu
Troy W Whitfield
Jonathan A R Gordon
Jason R Dobson
Phillip W L Tai
Andre J van Wijnen
Janet L Stein
Gary S Stein
Jane B Lian
University of Vermont · USBrown University · USMayo Clinic · USUniversity of Massachusetts Chan Medical School · US

Funding

Subnuclear Integration of Regulatory Signals Controlling Bone Cell FunctionP01AR048818 · NIAMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI STEIN, JANET L · 2002 to 2011
$14.0M
CONTROL OF OSTEOBLAST PROLIFERATION AND DIFFERENTIATIONR01AR039588 · NIAMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LIAN, JANE B., STEIN, GARY S. · 1990 to 2019
$8.0M
Synthesis of Osteocalcin in BoneR37DE012528 · NIDCR · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LIAN, JANE B. · 2008 to 2017
$5.0M
NIAMS NIH HHS P01 AR048818NIAMS NIH HHS R01 AR039588NIDCR NIH HHS R37 DE012528NIDCR NIH HHS R37 DE012528-24S1
6 · The paper itself

Abstract

backgroundOsteogenesis is a highly regulated developmental process and continues during the turnover and repair of mature bone. Runx2, the master regulator of osteoblastogenesis, directs a transcriptional program essential for bone formation through genetic and epigenetic mechanisms. While individual Runx2 gene targets have been identified, further insights into the broad spectrum of Runx2 functions required for osteogenesis are needed.

resultsBy performing genome-wide characterization of Runx2 binding at the three major stages of osteoblast differentiation--proliferation, matrix deposition and mineralization--we identify Runx2-dependent regulatory networks driving bone formation. Using chromatin immunoprecipitation followed by high-throughput sequencing over the course of these stages, we identify approximately 80,000 significantly enriched regions of Runx2 binding throughout the mouse genome. These binding events exhibit distinct patterns during osteogenesis, and are associated with proximal promoters and also non-promoter regions: upstream, introns, exons, transcription termination site regions, and intergenic regions. These peaks were partitioned into clusters that are associated with genes in complex biological processes that support bone formation. Using Affymetrix expression profiling of differentiating osteoblasts depleted of Runx2, we identify novel Runx2 targets including Ezh2, a critical epigenetic regulator; Crabp2, a retinoic acid signaling component; Adamts4 and Tnfrsf19, two remodelers of the extracellular matrix. We demonstrate by luciferase assays that these novel biological targets are regulated by Runx2 occupancy at non-promoter regions.

conclusionsOur data establish that Runx2 interactions with chromatin across the genome reveal novel genes, pathways and transcriptional mechanisms that contribute to the regulation of osteoblastogenesis.

Indexed as

Gene Expression Regulation, DevelopmentalGenomeOsteogenesisTranscription, GeneticAnimalsCell LineCore Binding Factor Alpha 1 SubunitGene Regulatory NetworksMiceOsteoblastsPromoter Regions, GeneticProtein BindingCore Binding Factor Alpha 1 SubunitRunx2 protein, mouse

Identifiers

PMID24655370
PMCPMC4056528
OpenAlexW2067129198

What OpenQuestion holds

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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.