Evidence map›Paper›PMID 18522731›Full record

ArticleBMC genomics2008

Identification of Pou5f1, Sox2, and Nanog downstream target genes with statistical confidence by applying a novel algorithm to time course microarray and genome-wide chromatin immunoprecipitation data.

Alexei A Sharov, Shinji Masui, Lioudmila V Sharova, Yulan Piao, Kazuhiro Aiba, Ryo Matoba, Li Xin, Hitoshi Niwa, Minoru S H Ko

Open access · goldAbstract read
In one paragraph

Article in BMC genomics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed, 2 pooled it
7.4field-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

105 citing papers in PubMed, 2 syntheses or guidelines pooled it, 164 citations in OpenAlex.

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  13. The Defects of Epigenetic Reprogramming in Dox-Dependent Porcine-iPSCs.International journal of molecular sciences · 2022
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45 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 1 institution in 1 country.

Alexei A SharovDevelopmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA. sharoval@mail.nih.gov
Shinji Masui
Lioudmila V Sharova
Yulan Piao
Kazuhiro Aiba
Ryo Matoba
Li Xin
Hitoshi Niwa
Minoru S H Ko
National Institute on Aging · US

Funding

Systematic analysis of gene regulatory networksZ01AG000656 · NIA · NATIONAL INSTITUTE ON AGING · PI KO, MINORU S · 1999 to 2008
$1.6M
Expression Profiling Of Mouse Embryonic Somatic Stem CeZ01AG000662 · NIA · NATIONAL INSTITUTE ON AGING · PI KO, MINORU S · 2001 to 2008
$1.1M
Transcription factor-manipulable mouse ES cell bankZ01AG000700 · NIA · NATIONAL INSTITUTE ON AGING · PI KO, MINORU · 1986 to 2008
$354k
Systematic identification of transcription factor binding sitesZ01AG000704 · NIA · NATIONAL INSTITUTE ON AGING · PI KO, MINORU · 1986 to 2008
$329k
EFFECT OF IN VIVO AND IN VITRO AGING ON NEOPLASTIC TRANSFORMATIONZ01AG000702 · NIA · NATIONAL INSTITUTE ON AGING · PI KO, MINORU · 1986 to 2008
$312k
Intramural NIH HHS Z01 AG000656
6 · The paper itself

Abstract

backgroundTarget genes of a transcription factor (TF) Pou5f1 (Oct3/4 or Oct4), which is essential for pluripotency maintenance and self-renewal of embryonic stem (ES) cells, have previously been identified based on their response to Pou5f1 manipulation and occurrence of Chromatin-immunoprecipitation (ChIP)-binding sites in promoters. However, many responding genes with binding sites may not be direct targets because response may be mediated by other genes and ChIP-binding site may not be functional in terms of transcription regulation.

resultsTo reduce the number of false positives, we propose to separate responding genes into groups according to direction, magnitude, and time of response, and to apply the false discovery rate (FDR) criterion to each group individually. Using this novel algorithm with stringent statistical criteria (FDR < 0.2) to a compendium of published and new microarray data (3, 6, 12, and 24 hr after Pou5f1 suppression) and published ChIP data, we identified 420 tentative target genes (TTGs) for Pou5f1. The majority of TTGs (372) were down-regulated after Pou5f1 suppression, indicating that the Pou5f1 functions as an activator of gene expression when it binds to promoters. Interestingly, many activated genes are potent suppressors of transcription, which include polycomb genes, zinc finger TFs, chromatin remodeling factors, and suppressors of signaling. Similar analysis showed that Sox2 and Nanog also function mostly as transcription activators in cooperation with Pou5f1.

conclusionWe have identified the most reliable sets of direct target genes for key pluripotency genes - Pou5f1, Sox2, and Nanog, and found that they predominantly function as activators of downstream gene expression. Thus, most genes related to cell differentiation are suppressed indirectly.

Indexed as

AlgorithmsGenomeOligonucleotide Array Sequence AnalysisAnimalsBinding SitesChromatin ImmunoprecipitationDNA-Binding ProteinsEmbryonic Stem CellsHMGB ProteinsHomeodomain ProteinsHumansMiceNanog Homeobox ProteinOctamer Transcription Factor-3SOXB1 Transcription FactorsTime FactorsDNA-Binding ProteinsHMGB ProteinsHomeodomain ProteinsNanog Homeobox ProteinNanog protein, mouseOctamer Transcription Factor-3Pou5f1 protein, mouseSOX2 protein, humanSox2 protein, mouseSOXB1 Transcription FactorsTranscription Factors

Identifiers

PMID18522731
PMCPMC2424064
OpenAlexW1982331566

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.