Epigenetic Mechanisms Underlying the Dynamic Expression of Cancer-Testis Genes, PAGE2, -2B and SPANX-B, during Mesenchymal-to-Epithelial Transition

Yilmaz-Ozcan, Sinem
Sade, Asli
Kucukkaraduman, Baris
Kaygusuz, Yasemin
Senses, Kerem Mert
Banerjee, Sreeparna
Cancer-testis (CT) genes are expressed in various cancers but not in normal tissues other than in cells of the germline. Although DNA demethylation of promoter-proximal CpGs of CT genes is linked to their expression in cancer, the mechanisms leading to demethylation are unknown. To elucidate such mechanisms we chose to study the Caco-2 colorectal cancer cell line during the course of its spontaneous differentiation in vitro, as we found CT genes, in particular PAGE2, -2B and SPANX-B, to be up-regulated during this process. Differentiation of these cells resulted in a mesenchymal-to-epithelial transition (MET) as evidenced by the gain of epithelial markers CDX2, Claudin-4 and E-cadherin, and a concomitant loss of mesenchymal markers Vimentin, Fibronectin-1 and Transgelin. PAGE2 and SPAN-X up-regulation was accompanied by an increase in Ten-eleven translocation-2 (TET2) expression and cytosine 5-hydroxymethylation as well as the disassociation of heterochromatin protein 1 and the polycomb repressive complex 2 protein EZH2 from promoter-proximal regions of these genes. Reversal of differentiation resulted in down-regulation of PAGE2, -2B and SPANX-B, and induction of epithelial-to-mesenchymal transition (EMT) markers, demonstrating the dynamic nature of CT gene regulation in this model.


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Sarac, Oemer Sinan; Atalay, Mehmet Volkan; Atalay, Rengül (Public Library of Science (PLoS), 2010-08-31)
Functional protein annotation is an important matter for in vivo and in silico biology. Several computational methods have been proposed that make use of a wide range of features such as motifs, domains, homology, structure and physicochemical properties. There is no single method that performs best in all functional classification problems because information obtained using any of these features depends on the function to be assigned to the protein. In this study, we portray a novel approach that combines ...
Novel BRCA2 pathogenic genotype and breast cancer phenotype discordance in monozygotic triplets
Duzkale, Neslihan; EYERCİ, NİLNUR; Oksuzoglu, Berna; Teker, Taner; Kandemir, Olcay (Elsevier BV, 2020-04-01)
BRCA1/2 genes with high-penetrance are tumor suppressor and tumor susceptibility genes that play important roles in the homologous recombination mechanism in DNA repair and increase breast cancer risk. Variants in BRCA1 or BRCA2 are the main causes of familial and early-onset breast cancer. This study investigated pathogenic variant belonging to the BRCA2 gene splice region in monozygotic triplets. A 44-year-old woman was diagnosed with breast cancer when she was 32 years old. Her monozygotic sister had a h...
Genome-wide analysis of gene expression profiling revealed that COP9 signalosome is essential for correct expression of Fe homeostasis genes in Arabidopsis
Eroğlu, Seçkin (Springer Science and Business Media LLC, 2017-10-01)
In plant cells, either excess or insufficient iron (Fe) concentration triggers stress responses, therefore it is strictly controlled. Proteasome-mediated degradation through ubiquitination of Fe homeostasis proteins has just become the focus of research in recent years. Deactivating ubiquitin ligases, COP9 signalosome has a central importance in the translational control of various stress responses. The aim of the study was to investigate COP9 signalosome in Fe deficiency response of Strategy I plants. In s...
Impaired toll like receptor-7 and 9 induced immune activation in chronic spinal cord injured patients contributes to immune dysfunction
Gucluler, Gozde; Adiguzel, Emre; Gungor, Bilgi; Kahraman, Tamer; Gürsel, Mayda; Yilmaz, Bilge; GÜRSEL, İHSAN (Public Library of Science (PLoS), 2017-02-07)
Reduced immune activation or immunosuppression is seen in patients withneurological diseases. Urinary and respiratory infections mainly manifested as septicemia and pneumonia are the most frequent complications following spinal cord injuries and they account for the majority of deaths. The underlying reason of these losses is believed to arise due to impaired immune responses to pathogens. Here, we hypothesized that susceptibility to infections of chronic spinal cord injured (SCI) patients might be due to i...
Autoinflammation in addition to combined immunodeficiency: SLC29A3 gene defect
Cagdas, Deniz; Surucu, Naz; TAN, ÇAĞMAN; ÖZGÜL, RIZA KÖKSAL; Akkaya-Ulum, Yeliz Z.; Aydinoglu, Ayse Tulay; Aytac, Selin; GÜMRÜK, FATMA; Balci-Hayta, Burcu; Balci-Peynircioglu, Banu; ÖZEN, SEZA; Gürsel, Mayda; Tezcan, Ilhan (Elsevier BV, 2020-05-01)
Introduction: H Syndrome is an autosomal recessive (AR) disease caused by defects in SLCA29A3 gene. This gene encodes the equilibrative nucleoside transporter, the protein which is highly expressed in spleen, lymph node and bone marrow. Autoinflammation and autoimmunity accompanies H Syndrome (HS).
Citation Formats
S. Yilmaz-Ozcan et al., “Epigenetic Mechanisms Underlying the Dynamic Expression of Cancer-Testis Genes, PAGE2, -2B and SPANX-B, during Mesenchymal-to-Epithelial Transition,” PLOS ONE, pp. 0–0, 2014, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/38540.