Evidence map›Paper›PMID 24472151›Full record

ArticleBMC molecular biology2014

Spdef deletion rescues the crypt cell proliferation defect in conditional Gata6 null mouse small intestine.

Boaz E Aronson, Kelly A Stapleton, Laurens A T M Vissers, Eva Stokhuijzen, Hanneke Bruijnzeel, Stephen D Krasinski

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.6field-weighted citation impact, top 32% 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

4 citing papers in PubMed, 9 citations in OpenAlex.

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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

6 authors at 5 institutions in 2 countries.

Boaz E Aronson
Kelly A Stapleton
Laurens A T M Vissers
Eva Stokhuijzen
Hanneke Bruijnzeel
Stephen D KrasinskiDivision of Gastroenterology and Nutrition, Department of Medicine, Children's Hospital Boston, and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA. stephen.krasinski@childrens.harvard.edu.
Academic Medical Center · NLBoston Children's Hospital · USEmma Kinderziekenhuis · NLHarvard University · USUniversity Medical Center Groningen · NL

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WAYNE I LENCER · 1986 to 2026
$32.4M
Regulation of Intestinal Gene ExpressionR01DK061382 · NIDDK · CHILDREN'S HOSPITAL BOSTON · PI KRASINSKI, STEPHEN D · 2003 to 2012
$3.0M
NIDDK NIH HHS 5P30-DK-34854NIDDK NIH HHS R01-DK-061382
6 · The paper itself

Abstract

backgroundGATA transcription factors are essential for self-renewal of the small intestinal epithelium. Gata4 is expressed in the proximal 85% of small intestine while Gata6 is expressed throughout the length of small intestine. Deletion of intestinal Gata4 and Gata6 results in an altered proliferation/differentiation phenotype, and an up-regulation of SAM pointed domain containing ETS transcription factor (Spdef), a transcription factor recently shown to act as a tumor suppressor. The goal of this study is to determine to what extent SPDEF mediates the downstream functions of GATA4/GATA6 in the small intestine. The hypothesis to be tested is that intestinal GATA4/GATA6 functions through SPDEF by repressing Spdef gene expression. To test this hypothesis, we defined the functions most likely regulated by the overlapping GATA6/SPDEF target gene set in mouse intestine, delineated the relationship between GATA6 chromatin occupancy and Spdef gene regulation in Caco-2 cells, and determined the extent to which prevention of Spdef up-regulation by Spdef knockout rescues the GATA6 phenotype in conditional Gata6 knockout mouse ileum.

resultsUsing publicly available profiling data, we found that 83% of GATA6-regulated genes are also regulated by SPDEF, and that proliferation/cancer is the function most likely to be modulated by this overlapping gene set. In human Caco-2 cells, GATA6 knockdown results in an up-regulation of Spdef gene expression, modeling our mouse Gata6 knockout data. GATA6 occupies a genetic locus located 40 kb upstream of the Spdef transcription start site, consistent with direct regulation of Spdef gene expression by GATA6. Prevention of Spdef up-regulation in conditional Gata6 knockout mouse ileum by the additional deletion of Spdef rescued the crypt cell proliferation defect, but had little effect on altered lineage differentiation or absorptive enterocytes gene expression.

conclusionSPDEF is a key, immediate downstream effecter of the crypt cell proliferation function of GATA4/GATA6 in the small intestine.

Indexed as

AnimalsCaco-2 CellsCell ProliferationGATA4 Transcription FactorGATA6 Transcription FactorGene Expression RegulationHumansIleumMiceMice, KnockoutProto-Oncogene Proteins c-etsTranscription FactorsUp-RegulationGATA4 Transcription FactorGATA6 Transcription FactorProto-Oncogene Proteins c-etsTranscription Factors

Identifiers

PMID24472151
PMCPMC3917371
OpenAlexW2141596199

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.