Evidence map›Paper›PMID 25398765›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015

The transcriptional corepressor MTGR1 regulates intestinal secretory lineage allocation.

Bobak Parang, Daniel Rosenblatt, Amanda D Williams, Mary K Washington, Frank Revetta, Sarah P Short, Vishruth K Reddy, Aubrey Hunt, Noah F Shroyer, Michael E Engel and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Transcriptional Regulation by ATOH1 and its Target SPDEF in the Intestine.Cellular and molecular gastroenterology and hepatology · 2017
    Article
  10. Article
  11. Review
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

12 authors at 6 institutions in 1 country.

Bobak Parang*Department of Medicine, Division of Gastroenterology, Departments of Cancer Biology, Pathology, Microbiology, and Immunology, and Biochemistry, Vanderbilt University, Nashville, Tennessee, USA; Department of Biology, Lipscomb University, Nashville, Tennessee, USA; Division of Pediatrics-Gastroenterology, Baylor University School of Medicine, Houston, Texas, USA; Division of Pediatric Hematology/Oncology, University of Utah, Salt Lake City, Utah; and **Vanderbilt Ingram Cancer Center, Veterans Affairs, Tennessee Valley Health Care System, Nashville, Tennessee, USA.
Daniel Rosenblatt*Department of Medicine, Division of Gastroenterology, Departments of Cancer Biology, Pathology, Microbiology, and Immunology, and Biochemistry, Vanderbilt University, Nashville, Tennessee, USA; Department of Biology, Lipscomb University, Nashville, Tennessee, USA; Division of Pediatrics-Gastroenterology, Baylor University School of Medicine, Houston, Texas, USA; Division of Pediatric Hematology/Oncology, University of Utah, Salt Lake City, Utah; and **Vanderbilt Ingram Cancer Center, Veterans Affairs, Tennessee Valley Health Care System, Nashville, Tennessee, USA.
Amanda D Williams*Department of Medicine, Division of Gastroenterology, Departments of Cancer Biology, Pathology, Microbiology, and Immunology, and Biochemistry, Vanderbilt University, Nashville, Tennessee, USA; Department of Biology, Lipscomb University, Nashville, Tennessee, USA; Division of Pediatrics-Gastroenterology, Baylor University School of Medicine, Houston, Texas, USA; Division of Pediatric Hematology/Oncology, University of Utah, Salt Lake City, Utah; and **Vanderbilt Ingram Cancer Center, Veterans Affairs, Tennessee Valley Health Care System, Nashville, Tennessee, USA.
Mary K Washington*Department of Medicine, Division of Gastroenterology, Departments of Cancer Biology, Pathology, Microbiology, and Immunology, and Biochemistry, Vanderbilt University, Nashville, Tennessee, USA; Department of Biology, Lipscomb University, Nashville, Tennessee, USA; Division of Pediatrics-Gastroenterology, Baylor University School of Medicine, Houston, Texas, USA; Division of Pediatric Hematology/Oncology, University of Utah, Salt Lake City, Utah; and **Vanderbilt Ingram Cancer Center, Veterans Affairs, Tennessee Valley Health Care System, Nashville, Tennessee, USA.
Frank Revetta*Department of Medicine, Division of Gastroenterology, Departments of Cancer Biology, Pathology, Microbiology, and Immunology, and Biochemistry, Vanderbilt University, Nashville, Tennessee, USA; Department of Biology, Lipscomb University, Nashville, Tennessee, USA; Division of Pediatrics-Gastroenterology, Baylor University School of Medicine, Houston, Texas, USA; Division of Pediatric Hematology/Oncology, University of Utah, Salt Lake City, Utah; and **Vanderbilt Ingram Cancer Center, Veterans Affairs, Tennessee Valley Health Care System, Nashville, Tennessee, USA.
Sarah P Short*Department of Medicine, Division of Gastroenterology, Departments of Cancer Biology, Pathology, Microbiology, and Immunology, and Biochemistry, Vanderbilt University, Nashville, Tennessee, USA; Department of Biology, Lipscomb University, Nashville, Tennessee, USA; Division of Pediatrics-Gastroenterology, Baylor University School of Medicine, Houston, Texas, USA; Division of Pediatric Hematology/Oncology, University of Utah, Salt Lake City, Utah; and **Vanderbilt Ingram Cancer Center, Veterans Affairs, Tennessee Valley Health Care System, Nashville, Tennessee, USA.
Vishruth K Reddy*Department of Medicine, Division of Gastroenterology, Departments of Cancer Biology, Pathology, Microbiology, and Immunology, and Biochemistry, Vanderbilt University, Nashville, Tennessee, USA; Department of Biology, Lipscomb University, Nashville, Tennessee, USA; Division of Pediatrics-Gastroenterology, Baylor University School of Medicine, Houston, Texas, USA; Division of Pediatric Hematology/Oncology, University of Utah, Salt Lake City, Utah; and **Vanderbilt Ingram Cancer Center, Veterans Affairs, Tennessee Valley Health Care System, Nashville, Tennessee, USA.
Aubrey Hunt*Department of Medicine, Division of Gastroenterology, Departments of Cancer Biology, Pathology, Microbiology, and Immunology, and Biochemistry, Vanderbilt University, Nashville, Tennessee, USA; Department of Biology, Lipscomb University, Nashville, Tennessee, USA; Division of Pediatrics-Gastroenterology, Baylor University School of Medicine, Houston, Texas, USA; Division of Pediatric Hematology/Oncology, University of Utah, Salt Lake City, Utah; and **Vanderbilt Ingram Cancer Center, Veterans Affairs, Tennessee Valley Health Care System, Nashville, Tennessee, USA.
Noah F Shroyer*Department of Medicine, Division of Gastroenterology, Departments of Cancer Biology, Pathology, Microbiology, and Immunology, and Biochemistry, Vanderbilt University, Nashville, Tennessee, USA; Department of Biology, Lipscomb University, Nashville, Tennessee, USA; Division of Pediatrics-Gastroenterology, Baylor University School of Medicine, Houston, Texas, USA; Division of Pediatric Hematology/Oncology, University of Utah, Salt Lake City, Utah; and **Vanderbilt Ingram Cancer Center, Veterans Affairs, Tennessee Valley Health Care System, Nashville, Tennessee, USA.
Michael E Engel*Department of Medicine, Division of Gastroenterology, Departments of Cancer Biology, Pathology, Microbiology, and Immunology, and Biochemistry, Vanderbilt University, Nashville, Tennessee, USA; Department of Biology, Lipscomb University, Nashville, Tennessee, USA; Division of Pediatrics-Gastroenterology, Baylor University School of Medicine, Houston, Texas, USA; Division of Pediatric Hematology/Oncology, University of Utah, Salt Lake City, Utah; and **Vanderbilt Ingram Cancer Center, Veterans Affairs, Tennessee Valley Health Care System, Nashville, Tennessee, USA.
Scott W Hiebert*Department of Medicine, Division of Gastroenterology, Departments of Cancer Biology, Pathology, Microbiology, and Immunology, and Biochemistry, Vanderbilt University, Nashville, Tennessee, USA; Department of Biology, Lipscomb University, Nashville, Tennessee, USA; Division of Pediatrics-Gastroenterology, Baylor University School of Medicine, Houston, Texas, USA; Division of Pediatric Hematology/Oncology, University of Utah, Salt Lake City, Utah; and **Vanderbilt Ingram Cancer Center, Veterans Affairs, Tennessee Valley Health Care System, Nashville, Tennessee, USA.
Christopher S Williams*Department of Medicine, Division of Gastroenterology, Departments of Cancer Biology, Pathology, Microbiology, and Immunology, and Biochemistry, Vanderbilt University, Nashville, Tennessee, USA; Department of Biology, Lipscomb University, Nashville, Tennessee, USA; Division of Pediatrics-Gastroenterology, Baylor University School of Medicine, Houston, Texas, USA; Division of Pediatric Hematology/Oncology, University of Utah, Salt Lake City, Utah; and **Vanderbilt Ingram Cancer Center, Veterans Affairs, Tennessee Valley Health Care System, Nashville, Tennessee, USA christopher.williams@vanderbilt.edu.
Vanderbilt University · USBaylor School · USLipscomb University · USUniversity of Utah · USVanderbilt Health · USVA Tennessee Valley Healthcare System · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
The Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4M
Understanding and Controlling p120 Dysfunction in CRCP50CA095103 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI COFFEY, ROBERT J. · 2002 to 2017
$33.6M
Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007347 · NIGMS · VANDERBILT UNIVERSITY · PI WILLIAMS, CHRISTOPHER S. · 1985 to 2023
$26.3M
Regulation of transcription and tumor suppression by MTG family membersR01CA178030 · NCI · VANDERBILT UNIVERSITY · PI HIEBERT, SCOTT W · 2014 to 2018
$1.8M
Selenium in gastrointestinal inflammatory diseasesR01DK099204 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WILLIAMS, CHRISTOPHER S. · 2014 to 2018
$1.8M
KLF5 regulation of intestinal development and stem cell homeostasis.R01DK092306 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI SHROYER, NOAH FREEMAN · 2011 to 2014
$1.6M
The role of ATOH1 as a tumor suppressor in colorectal cancerR01CA142826 · NCI · CINCINNATI CHILDRENS HOSP MED CTR · PI SHROYER, NOAH FREEMAN · 2010 to 2014
$1.5M
Regulation of MTG16 and Notch signaling in hematopoiesisK08DK080190 · NIDDK · VANDERBILT UNIVERSITY · PI ENGEL, MICHAEL E · 2010 to 2014
$728k
The role of MTGR1 in intestinal biology and inflammationK08DK080221 · NIDDK · VANDERBILT UNIVERSITY · PI WILLIAMS, CHRISTOPHER S. · 2008 to 2012
$705k
The Role of BVES in Intestinal Repair Programs and Inflammatory Bowel DiseaseF30DK096718 · NIDDK · VANDERBILT UNIVERSITY · PI PARANG, BOBAK · 2012 to 2015
$106k
BLRD VA I01 BX001426NCATS NIH HHS UL1 TR000445NCATS NIH HHS UL1TR000445NCI NIH HHS P30 CA068485NCI NIH HHS P30CA068485NCI NIH HHS P50 CA095103NCI NIH HHS P50CA095103NCI NIH HHS R01 CA142826NCI NIH HHS R01CA1428260NCI NIH HHS R01 CA178030NCI NIH HHS R01CA178030NIDDK NIH HHS F30 DK096718NIDDK NIH HHS F30DK096718-01NIDDK NIH HHS K08 DK080190NIDDK NIH HHS K08DK080190NIDDK NIH HHS K08 DK080221NIDDK NIH HHS K08DK080221NIDDK NIH HHS P30 DK058404NIDDK NIH HHS P30DK058404NIDDK NIH HHS R01 DK092306NIDDK NIH HHS R01DK092306NIDDK NIH HHS R01 DK099204NIGMS NIH HHS T32 GM007347NIGMS NIH HHS T32 GM07347
6 · The paper itself

Abstract

Notch signaling largely determines intestinal epithelial cell fate. High Notch activity drives progenitors toward absorptive enterocytes by repressing secretory differentiation programs, whereas low Notch permits secretory cell assignment. Myeloid translocation gene-related 1 (MTGR1) is a transcriptional corepressor in the myeloid translocation gene/Eight-Twenty-One family. Given that Mtgr1(-/-) mice have a dramatic reduction of intestinal epithelial secretory cells, we hypothesized that MTGR1 is a key repressor of Notch signaling. In support of this, transcriptome analysis of laser capture microdissected Mtgr1(-/-) intestinal crypts revealed Notch activation, and secretory markers Mucin2, Chromogranin A, and Growth factor-independent 1 (Gfi1) were down-regulated in Mtgr1(-/-) whole intestines and Mtgr1(-/-) enteroids. We demonstrate that MTGR1 is in a complex with Suppressor of Hairless Homolog, a key Notch effector, and represses Notch-induced Hairy/Enhancer of Split 1 activity. Moreover, pharmacologic Notch inhibition using a γ-secretase inhibitor (GSI) rescued the hyperproliferative baseline phenotype in the Mtgr1(-/-) intestine and increased production of goblet and enteroendocrine lineages in Mtgr1(-/-) mice. GSI increased Paneth cell production in wild-type mice but failed to do so in Mtgr1(-/-) mice. We determined that MTGR1 can interact with GFI1, a transcriptional corepressor required for Paneth cell differentiation, and repress GFI1 targets. Overall, the data suggest that MTGR1, a transcriptional corepressor well characterized in hematopoiesis, plays a critical role in intestinal lineage allocation.

Indexed as

Cell LineageAmyloid Precursor Protein SecretasesAnimalsApoptosisBlotting, WesternCell DifferentiationCell ProliferationCells, CulturedEpithelial CellsFlow CytometryImmunoenzyme TechniquesImmunoprecipitationIntestinal MucosaIntestinesMiceMice, KnockoutAmyloid Precursor Protein SecretasesCBFA2T2 myeloid-transforming gene-related proteinProtease InhibitorsReceptors, NotchRepressor ProteinsRNA, MessengerCBFA2T2Notch signalingPaneth cells

Identifiers

PMID25398765
PMCPMC4763883
OpenAlexW2123857063

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Registered trials

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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.