A Novel CDX2 Isoform Regulates Alternative Splicing

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Aug 8

PMID 25101906

Citations 3

Authors

Matthew E Witek

Adam E Snook

Jieru E Lin

Erik S Blomain

Bo Xiang

Michael S Magee

Michael Magee

Scott A Waldman

Affiliations

Soon will be listed here.

Abstract

Gene expression is a dynamic and coordinated process coupling transcription with pre-mRNA processing. This regulation enables tissue-specific transcription factors to induce expression of specific transcripts that are subsequently amplified by alternative splicing allowing for increased proteome complexity and functional diversity. The intestine-specific transcription factor CDX2 regulates development and maintenance of the intestinal epithelium by inducing expression of genes characteristic of the mature enterocyte phenotype. Here, sequence analysis of CDX2 mRNA from colonic mucosa-derived tissues revealed an alternatively spliced transcript (CDX2/AS) that encodes a protein with a truncated homeodomain and a novel carboxy-terminal domain enriched in serine and arginine residues (RS domain). CDX2 and CDX2/AS exhibited distinct nuclear expression patterns with minimal areas of co-localization. CDX2/AS did not activate the CDX2-dependent promoter of guanylyl cyclase C nor inhibit transcriptional activity of CDX2. Unlike CDX2, CDX2/AS co-localized with the putative splicing factors ASF/SF2 and SC35. CDX2/AS altered splicing patterns of CD44v5 and Tra2-β1 minigenes in Lovo colon cancer cells independent of CDX2 expression. These data demonstrate unique dual functions of the CDX2 gene enabling it to regulate gene expression through both transcription (CDX2) and pre-mRNA processing (CDX2/AS).

Citing Articles

Fine-tuning and autoregulation of the intestinal determinant and tumor suppressor homeobox gene CDX2 by alternative splicing.

Balbinot C, Vanier M, Armant O, Nair A, Penichon J, Soret C Cell Death Differ. 2017; 24(12):2173-2186.

PMID: 28862703 PMC: 5686355. DOI: 10.1038/cdd.2017.140.

Targeted CDX2 expression inhibits aggressive phenotypes of colon cancer cells in vitro and in vivo.

Zheng J, He S, Qi J, Wang X, Yu J, Wu Y Int J Oncol. 2017; 51(2):478-488.

PMID: 28627695 PMC: 5505129. DOI: 10.3892/ijo.2017.4040.

Extending the functions of the homeotic transcription factor Cdx2 in the digestive system through nontranscriptional activities.

Freund J, Duluc I, Reimund J, Gross I, Domon-Dell C World J Gastroenterol. 2015; 21(5):1436-43.

PMID: 25663763 PMC: 4316086. DOI: 10.3748/wjg.v21.i5.1436.

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