Oct1 is a switchable, bipotential stabilizer of repressed and inducible transcriptional states.
Little is known regarding how the Oct1 transcription factor regulates target gene expression. Using murine fibroblasts and two target genes, Polr2a and Ahcy, we show that Oct1 recruits the Jmjd1a/KDM3A lysine demethylase to catalyze the removal of the inhibitory histone H3K9 dimethyl mark and block repression. Using purified murine T cells and the Il2 target locus, and a colon cancer cell line and the Cdx2 target locus, we show that Oct1 recruits the NuRD chromatin-remodeling complex to promote a repressed state, but in a regulated manner can switch to a different capacity and mediate Jmjd1a recruitment to block repression. These findings indicate that Oct1 maintains repression through a mechanism involving NuRD and maintains poised gene expression states through an antirepression mechanism involving Jmjd1a. We propose that, rather than acting as a primary trigger of gene activation or repression, Oct1 is a switchable stabilizer of repressed and inducible states.
Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
Arvind
A
Shakya
Jinsuk
J
Kang
Jeffrey
J
Chumley
Matthew A
MA
Williams
Dean
D
Tantin
D000818:Animals; D001483:Base Sequence; D000071616:CDX2 Transcription Factor; D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000378:metabolism; D056426:Genetic Loci / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D027702:Organic Cation Transporter 1 / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D027702:Organic Cation Transporter 1; D056484:Jumonji Domain-Containing Histone Demethylases; C511045:Kdm3a protein, mouse; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D013755:Tetradecanoylphorbol Acetate