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Series GSE67790 Query DataSets for GSE67790
Status Public on Jan 01, 2016
Title Smyd3 is a transcriptional potentiator of multiple cancer-promoting genes and required for liver or colon cancer development
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Smyd3 is a histone methyltransferase implicated in tumorigenesis. Here we show that Smyd3 expression in mice is required but not sufficient for chemically induced liver and colon cancer formation. In these organs Smyd3 is functioning in the nucleus as a direct transcriptional activator of several key genes involved in cell proliferation, epithelial-mesenchymal transition, JAK/Stat3 oncogenic pathways, as well as of the c-myc and b-catenin oncogenes. Smyd3 specifically interacts with H3K4Me3-modified histone tails and is recruited to the core promoter regions of many but not all active genes. Smyd3 binding density on target genes positively correlates with increased RNA Pol-II density and transcriptional outputs. The results suggest that Smyd3 is an essential transcriptional potentiator of a multitude of cancer-related genes.
 
Overall design Standard Smyd3-deficient (Smyd3-KO) mice were generated using gene-trap ES cell clones (AS0527 from International Gene Trap Consortium), in which a selection cassette, containing the splice acceptor site from mouse EN2 exon 2 followed by the beta-galactosidase and neomycin resistance gene fusion gene and the SV40 polyadenylation sequence was inserted into the 5th intron of the Smyd3 gene. The resulting mice were devoid of Smyd3 mRNA and protein in all tissues, including liver and colon. For the generation of Smyd3-Tg mice the open reading frame of the mouse Smyd3 cDNA, which contained 3 Flag epitopes at the 3’ end was inserted into the StuI site of the pTTR1-ExV3 plasmid (Yan et al, 1990). The 6.8 kb HindIII fragment containing the mouse transthyretin enhancer/promoter, intron 1, Smyd3 cDNA, three Flag epitopes and SV40 poly-A site was used to microinject C57Bl/6 fertilized oocytes. Founder animals were identified by Southern blotting and crossed with F1 mice to generate lines. Specific overexpression in the liver was tested by RT-PCR analysis in different tissues.
 
Contributor(s) Sarris M, Moulos P, Haroniti A, Talianidis I
Citation(s) 26908355
Submission date Apr 13, 2015
Last update date May 15, 2019
Contact name Iannis Talianidis
E-mail(s) talianid@imbb.forth.gr
Organization name Foundation for Research and Technology - Hellas
Department Institute of Molecular Biology and Biotechnology
Street address 100 N. Plastira Str
City Vassilika Vouton, Herakleion
State/province Crete
ZIP/Postal code 70013
Country Greece
 
Platforms (1)
GPL18635 Ion Torrent Proton (Mus musculus)
Samples (24)
GSM1656142 WT RNAseq_replicate 1
GSM1656143 WT RNAseq_replicate 2
GSM1656144 WT RNAseq_replicate 3
Relations
BioProject PRJNA280944
SRA SRP057101

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Supplementary file Size Download File type/resource
GSE67790_H3K4me3_Smyd3KO_ChIP_enriched_regions.bed.gz 227.3 Kb (ftp)(http) BED
GSE67790_H3K4me3_WT_ChIP_enriched_regions.bed.gz 202.8 Kb (ftp)(http) BED
GSE67790_RAW.tar 1.5 Gb (http)(custom) TAR (of BIGWIG, TXT)
GSE67790_Smyd3_ChIP_peaks.bed.gz 346.0 Kb (ftp)(http) BED
GSE67790_WT_DEN-WT_Smyd3KO_DEN-Smyd3KO_norm_counts.txt.gz 1.2 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data provided as supplementary file

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