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Ligand-dependent corepressor contributes to transcriptional repression by C2H2 zinc-finger transcription factor ZBRK1 through association with KRAB-associated protein-1.

Calderon MR, Verway M, Benslama RO, Birlea M, Bouttier M, Dimitrov V, Mader S, White JH - Nucleic Acids Res. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, McGill University, Montreal, QC, Canada.

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FGF2 expression is inversely correlated with KAP-1 and ZBRK1 expression in the TGCA data set of breast invasive carcinoma. (Top) Gene expression in breast invasive carcinoma was normalized to normal control tissue, and samples were gated for high and low expressions of FGF2, where red indicates upregulation and blue indicates downregulation. (Middle) Box-plot of this analysis of these samples demonstrates that the mean expression for KAP-1 and ZBRK1 relative to control tissue was inversely correlated with the expression of FGF2 in both sample populations. (Bottom) In samples that expressed high FGF2, the mean expression of KAP-1 and ZBRK1 was negative (values indicated on bar graph) relative to control tissue and statistically significant at P = 0.001 as determined by student's t-test.
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Figure 8: FGF2 expression is inversely correlated with KAP-1 and ZBRK1 expression in the TGCA data set of breast invasive carcinoma. (Top) Gene expression in breast invasive carcinoma was normalized to normal control tissue, and samples were gated for high and low expressions of FGF2, where red indicates upregulation and blue indicates downregulation. (Middle) Box-plot of this analysis of these samples demonstrates that the mean expression for KAP-1 and ZBRK1 relative to control tissue was inversely correlated with the expression of FGF2 in both sample populations. (Bottom) In samples that expressed high FGF2, the mean expression of KAP-1 and ZBRK1 was negative (values indicated on bar graph) relative to control tissue and statistically significant at P = 0.001 as determined by student's t-test.

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.


Ligand-dependent corepressor contributes to transcriptional repression by C2H2 zinc-finger transcription factor ZBRK1 through association with KRAB-associated protein-1.

Calderon MR, Verway M, Benslama RO, Birlea M, Bouttier M, Dimitrov V, Mader S, White JH - Nucleic Acids Res. (2014)

FGF2 expression is inversely correlated with KAP-1 and ZBRK1 expression in the TGCA data set of breast invasive carcinoma. (Top) Gene expression in breast invasive carcinoma was normalized to normal control tissue, and samples were gated for high and low expressions of FGF2, where red indicates upregulation and blue indicates downregulation. (Middle) Box-plot of this analysis of these samples demonstrates that the mean expression for KAP-1 and ZBRK1 relative to control tissue was inversely correlated with the expression of FGF2 in both sample populations. (Bottom) In samples that expressed high FGF2, the mean expression of KAP-1 and ZBRK1 was negative (values indicated on bar graph) relative to control tissue and statistically significant at P = 0.001 as determined by student's t-test.
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Figure 8: FGF2 expression is inversely correlated with KAP-1 and ZBRK1 expression in the TGCA data set of breast invasive carcinoma. (Top) Gene expression in breast invasive carcinoma was normalized to normal control tissue, and samples were gated for high and low expressions of FGF2, where red indicates upregulation and blue indicates downregulation. (Middle) Box-plot of this analysis of these samples demonstrates that the mean expression for KAP-1 and ZBRK1 relative to control tissue was inversely correlated with the expression of FGF2 in both sample populations. (Bottom) In samples that expressed high FGF2, the mean expression of KAP-1 and ZBRK1 was negative (values indicated on bar graph) relative to control tissue and statistically significant at P = 0.001 as determined by student's t-test.
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, McGill University, Montreal, QC, Canada.

Show MeSH
Related in: MedlinePlus