Evidence map›Paper›PMID 21464207›Full record

ArticleMolecular and cellular biology2011

Genome-wide approaches reveal functional interleukin-4-inducible STAT6 binding to the vascular cell adhesion molecule 1 promoter.

Hideto Tozawa, Yasuharu Kanki, Jun-ichi Suehiro, Shuichi Tsutsumi, Takahide Kohro, Youichiro Wada, Hiroyuki Aburatani, William C Aird, Tatsuhiko Kodama, Takashi Minami

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In one paragraph

Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 14% 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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

  1. Pooled it
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  13. A hypothesis-effect of T cell epitope fusion peptide specific immunotherapy on signal transduction.International journal of clinical and experimental medicine · 2015
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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

10 authors at 2 institutions in 2 countries.

Hideto TozawaResearch Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904, Japan.
Yasuharu Kanki
Jun-ichi Suehiro
Shuichi Tsutsumi
Takahide Kohro
Youichiro Wada
Hiroyuki Aburatani
William C Aird
Tatsuhiko Kodama
Takashi Minami
The University of Tokyo · JPHarvard University · US

Funding

VASCULAR TOPOGRAPHY OF CD39/NTPDASESP01HL076540 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI AIRD, WILLIAM C · 2004 to 2014
$20.3M
VEGF, Transcriptional Networks and Vascular InflammationR01HL082927 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI AIRD, WILLIAM C · 2007 to 2010
$1.5M
NHLBI NIH HHS HL076540NHLBI NIH HHS HL082927NHLBI NIH HHS P01 HL076540NHLBI NIH HHS R01 HL082927
6 · The paper itself

Abstract

Endothelial cell activation and dysfunction underlie many vascular disorders, including atherosclerosis and inflammation. Here, we show that interleukin-4 (IL-4) markedly induced vascular cell adhesion molecule 1 (VCAM-1), both in cultured endothelial cells and in the intact endothelium in mice. Combined treatment with IL-4 and tumor necrosis factor alpha (TNF-α) resulted in further, sustained induction of VCAM-1 expression. IL-4-mediated induction of VCAM-1 and secondary monocyte adhesion was predominantly regulated by the transcription factor STAT6. Genome-wide survey of IL-4-mediated STAT6 binding from sequential chromatin-immunoprecipitation with deep sequencing (chromatin immunoprecipitation sequencing [ChIP-seq]) in endothelial cells revealed regions of transient and sustained transcription factor binding. Through the combination of DNA microarrays and ChIP-seq at the same time points, the majority of IL-4-responsive genes were shown to be STAT6 dependent and associated with direct STAT6 binding to their promoter. IL-4-mediated stable binding of STAT6 led to sustained target gene expression. Moreover, our strategy led to the identification of a novel functionally important STAT6 binding site within 16 kb upstream of the VCAM-1 gene. Taken together, these findings support a critical role for STAT6 in mediating IL-4 signal transduction in endothelial cells. Identification of a novel IL-4-mediated VCAM-1 enhancer may provide a foundation for targeted therapy in vascular disease.

Indexed as

Promoter Regions, GeneticRegulatory Sequences, Nucleic AcidAnimalsBinding SitesCell AdhesionChromatin ImmunoprecipitationEndothelial CellsEndotheliumGene ExpressionHEK293 CellsHumansInterleukin-4MiceMice, Inbred C57BLMonocytesOligonucleotide Array Sequence AnalysisInterleukin-4STAT6 Transcription FactorTumor Necrosis Factor-alphaVascular Cell Adhesion Molecule-1

Identifiers

PMID21464207
PMCPMC3133239
OpenAlexW2144011204

What OpenQuestion holds

Textmetadata
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.