The Myc 3'wnt-responsive element regulates homeostasis and regeneration in the mouse intestinal tract

Wesley M. Konsavage, Ge Jin, Gregory Yochum

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The Wnt/β-catenin signaling pathway controls cellular proliferation in the intestines. In response to Wnt, β-catenin transits into the nucleus and associates with members of the T-cell factor (TCF) family of transcription factors. β-Catenin/TCF complexes bind Wnt responsive DNA elements (WREs) to activate target gene expression. The c-MYC proto-oncogene (MYC) is a direct target of β-catenin/TCF complexes. We recently identified the MYC 3'WRE, which maps 1.4-kb downstream from the MYC transcription stop site. To investigate the role of the Myc 3'WRE in the intestines, we generated a mouse model with a germ line deletion of this element. The intestinal architecture was largely preserved in knockout mice; however, removal of the Myc 3'WRE compromised the crypt microenvironment. In comparison to wild-type intestines, knockout intestines contained an increased number of proliferative cells and a reduced number of differentiated cells comprising both absorptive and secretory lineages. Using a model of colitis, we found that knockout colons repaired more rapidly during the recovery period of the protocol. These results indicate that regulation of MYC expression through the Myc 3= WRE contributes to intestinal homeostasis. Furthermore, our study implicates MYC as an important regulator of intestinal regeneration following injury.

Original languageEnglish (US)
Pages (from-to)3891-3902
Number of pages12
JournalMolecular and cellular biology
Volume32
Issue number19
DOIs
StatePublished - Oct 1 2012

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Catenins
Regeneration
TCF Transcription Factors
Homeostasis
Intestines
DNA
Cell Count
Wnt Signaling Pathway
Proto-Oncogenes
Colitis
Knockout Mice
Germ Cells
Colon
Transcription Factors
Cell Proliferation
Gene Expression
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

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abstract = "The Wnt/β-catenin signaling pathway controls cellular proliferation in the intestines. In response to Wnt, β-catenin transits into the nucleus and associates with members of the T-cell factor (TCF) family of transcription factors. β-Catenin/TCF complexes bind Wnt responsive DNA elements (WREs) to activate target gene expression. The c-MYC proto-oncogene (MYC) is a direct target of β-catenin/TCF complexes. We recently identified the MYC 3'WRE, which maps 1.4-kb downstream from the MYC transcription stop site. To investigate the role of the Myc 3'WRE in the intestines, we generated a mouse model with a germ line deletion of this element. The intestinal architecture was largely preserved in knockout mice; however, removal of the Myc 3'WRE compromised the crypt microenvironment. In comparison to wild-type intestines, knockout intestines contained an increased number of proliferative cells and a reduced number of differentiated cells comprising both absorptive and secretory lineages. Using a model of colitis, we found that knockout colons repaired more rapidly during the recovery period of the protocol. These results indicate that regulation of MYC expression through the Myc 3= WRE contributes to intestinal homeostasis. Furthermore, our study implicates MYC as an important regulator of intestinal regeneration following injury.",
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The Myc 3'wnt-responsive element regulates homeostasis and regeneration in the mouse intestinal tract. / Konsavage, Wesley M.; Jin, Ge; Yochum, Gregory.

In: Molecular and cellular biology, Vol. 32, No. 19, 01.10.2012, p. 3891-3902.

Research output: Contribution to journalArticle

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