ArticleNucleic acids research2012
An insulator loop resides between the synthetically interacting elements of the human/rat conserved breast cancer susceptibility locus MCS5A/Mcs5a.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Integrating molecular pathway with genome-wide association data for causality identification in breast cancer.Discover oncology · 2024Article
- Deletion of the murine ortholog of the 8q24 gene desert has anti-cancer effects in transgenic mammary cancer models.BMC cancer · 2018Article
- The Non-coding Mammary Carcinoma Susceptibility Locus, Mcs5c, Regulates Pappa Expression via Age-Specific Chromatin Folding and Allele-Dependent DNA Methylation.PLoS genetics · 2016Article
- Small molecule therapeutics targeting F-box proteins in cancer.Seminars in cancer biology · 2016Review
- Deregulation of F-box proteins and its consequence on cancer development, progression and metastasis.Seminars in cancer biology · 2016Review
- Differential 12-O-Tetradecanoylphorbol-13-acetate-induced activation of rat mammary carcinoma susceptibility Fbxo10 variant promoters via a PKC-AP1 pathway.Molecular carcinogenesis · 2015Article
- Human MCS5A1 candidate breast cancer susceptibility gene FBXO10 is induced by cellular stress and correlated with lens epithelium-derived growth factor (LEDGF).Molecular carcinogenesis · 2014Article
- Roles of F-box proteins in cancer.Nature reviews. Cancer · 2014Review
- The gene desert mammary carcinoma susceptibility locus Mcs1a regulates Nr2f1 modifying mammary epithelial cell differentiation and proliferation.PLoS genetics · 2013Article
- Analysis of long-range chromatin interactions using Chromosome Conformation Capture.Methods (San Diego, Calif.) · 2012Article
- Article
- Rats: gnawing through the barriers to understanding genetic susceptibility and breast cancer.Breast cancer research : BCR · 2011Article
- The non-protein coding breast cancer susceptibility locus Mcs5a acts in a non-mammary cell-autonomous fashion through the immune system and modulates T-cell homeostasis and functions.Breast cancer research : BCR · 2011Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Many low-penetrance breast cancer susceptibility loci are found to be located in non-protein-coding regions, suggesting their involvement in gene expression regulation. We identified the human/rat-conserved breast cancer susceptibility locus MCS5A/Mcs5a. This locus has been shown to act in a non-mammary cell-autonomous fashion through the immune system. The resistant Mcs5a allele from the Wistar-Kyoto (WKy) rat strain consists of two non-protein-coding genetic elements that must be located on the same chromosome to elicit the phenotype. In this study, we show the presence of a conserved higher order chromatin structure in MCS5A/Mcs5a located in between the synthetically interacting genetic elements. The looped elements are shown to be bound by CTCF and cohesin. We identify the downregulation of Fbxo10 expression in T cells as a strong candidate mechanism through which the interacting genetic elements of the resistant Mcs5a allele modulate mammary carcinoma susceptibility. Finally, we show that the human MCS5A polymorphisms associated with breast cancer risk are located at both sides of the looped structure and functionally interact to downregulate transcriptional activity, similar to rat Mcs5a. We propose a mechanistic model for MCS5a/Mcs5a in which a CTCF-mediated insulator loop encompassing the TOMM5/Tomm5 gene, resides in between and brings into closer physical proximity the synthetically and functionally interacting resistant genetic variants.
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