Ligand-dependent corepressor contributes to transcriptional repression by C2H2 zinc-finger transcription factor ZBRK1 through association with KRAB-associated protein-1.
Bottom Line: We identified a novel interaction between ligand-dependent corepressor (LCoR) and the corepressor KRAB-associated protein-1 (KAP-1).We propose that ZBRK1, KAP-1 and LCoR form a transcriptional complex that silences gene expression, in particular FGF2, which maintains breast cell viability.Given the broad expression patterns of both LCoR and KAP-1 during development and in the adult, this complex may have several regulatory functions that extend beyond cell survival, mediated by interactions with ZBRK1 or other C2H2 zinc-finger proteins.
Affiliation: Department of Physiology, McGill University, Montreal, QC, Canada.Show MeSH
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Mentions: A publicly available The Cancer Genome Atlas (TCGA) data set [breast invasive carcinoma (BRCA)-UNC-IlluminaHiSeq_RNAseq, N = 1106] was downloaded via the Cancer Genome Atlas data portal (https://tcga-data.nci.nih.gov/tcga/). We analyzed the TGCA data using the UCSC Cancer Browser. Normalizing the expression of genes in the data set to normal tissue, we saw that FGF2 expression is reduced in breast invasive carcinoma, while TRIM28 is up, and ZNF350 and LCoR show no difference (not shown). Gating on breast cancer cells that have a low or high expression of FGF2, we can see that the distribution of KAP-1 and ZBRK-1 expression, but not LCoR, is inversely correlated with the expression of FGF2 in the samples of breast invasive carcinoma (Figure 8). In cases where FGF2 was elevated, the mean expression of KAP-1 and TRIM28 was negative, and the statistical significance of this inverse correlation was significant to –log(−3) or P = 0.001 as determined by student's t-test.
Affiliation: Department of Physiology, McGill University, Montreal, QC, Canada.