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Series GSE124544 Query DataSets for GSE124544
Status Public on Apr 02, 2019
Title Kaiso is required for MTG16-dependent effects on colitis-associated carcinoma
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The myeloid translocation gene family member MTG16 is a transcriptional corepressor that relies on the DNA-binding ability of other proteins to determine specificity. One such protein is the ZBTB family member Kaiso, and the MTG16:Kaiso interaction is necessary for repression of Kaiso target genes such as matrix metalloproteinase-7. Using the azoxymethane and dextran sodium sulfate (AOM/DSS) murine model of colitis-associated carcinoma, we previously determined that MTG16 loss accelerates tumorigenesis and inflammation. However, it was unknown whether this effect was modified by Kaiso-dependent transcriptional repression. To test for a genetic interaction between MTG16 and Kaiso in inflammatory carcinogenesis, we subjected single and double knockout (DKO) mice to the AOM/DSS protocol. Mtg16-/- mice demonstrated increased colitis and tumor burden; in contrast, disease severity in Kaiso-/- mice was equivalent to wild type controls. Surprisingly, Kaiso deficiency in the context of MTG16 loss reversed injury and pro-tumorigenic responses in the intestinal epithelium following AOM/DSS treatment, and tumor numbers were returned to near to wild type levels. Transcriptomic analysis of non-tumor colon tissue demonstrated that changes induced by MTG16 loss were widely mitigated by concurrent Kaiso loss, and DKO mice demonstrated downregulation of metabolism and cytokine-associated gene sets with concurrent activation of DNA damage checkpoint pathways as compared with Mtg16-/-. Further, Kaiso knockdown in intestinal enteroids reduced stem- and WNT-associated phenotypes, thus abrogating the induction of these pathways observed in Mtg16-/- samples. Together, these data suggest that Kaiso modifies MTG16-driven inflammation and tumorigenesis and suggests that Kaiso deregulation contributes to MTG16-dependent colitis and CAC phenotypes.
Overall design Adjacent normal colon tissue was harvested from WT, Kaiso-/-, Mtgt16-/-, and double knockout mice after conclusion of the AOM/DSS treatment protocol. 3 samples were used per genotype
Contributor(s) Short SP, Williams CS
Citation(s) 30858547
Submission date Jan 02, 2019
Last update date Apr 02, 2019
Contact name Christopher Williams
Phone 6153220320
Organization name Vanderbilt University Medical Center
Street address 2215-B Garland Ave, 1075 MRB4
City Nashville
State/province Tennessee
ZIP/Postal code 37232
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (12)
GSM3536205 WT colon 1
GSM3536206 WT colon 2
GSM3536207 WT colon 3
BioProject PRJNA512466
SRA SRP174997

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Supplementary file Size Download File type/resource
GSE124544_16KO_DKO_gene_exp.xlsx 2.3 Mb (ftp)(http) XLSX
GSE124544_DKO_vs_WT.xlsx 2.5 Mb (ftp)(http) XLSX
GSE124544_WT_v_KaisoKO_gene_exp.xlsx 2.4 Mb (ftp)(http) XLSX
GSE124544_wt_16KO_gene_exp.xlsx 2.4 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record

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