The epigenetic factor BORIS/CTCFL regulates the NOTCH3 gene expression in cancer cells
| العنوان: | The epigenetic factor BORIS/CTCFL regulates the NOTCH3 gene expression in cancer cells |
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| المؤلفون: | Fabio Ciccarone, Isabella Screpanti, Paola Caiafa, Sabina Chiaretti, Michele Zampieri, Claudio Passananti, Rocco Palermo, Daniela Nocchia, Claudio Talora, Samantha Cialfi |
| المساهمون: | Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP), Department of Cellular Biotechnologies and Haematology, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]-Faculty of Pharmacy & Medicine, Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia (IIT), Department of Molecular Medicine, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]-Faculty of Pharmacy and Medicine, Institute of Molecular Biology and Pathology, CNR, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], This research was supported by grants from the Italian Ministry of University and Research (MIUR) (P.C.: FIRB-RBIN06E9Z8_003, I.S.: FIRB-RBAP11WCRZ, I.S.: PRIN-2010MCLPLB), Sapienza University of Rome (M.Z.: C26A134WJ2, M.Z.: C26A12PN9T) and the Italian Association for Cancer Research (AIRC) (I.S.:IG 13314)., Institut Pasteur - Fondation Cenci Bolognetti, Réseau International des Instituts Pasteur - Institut Pasteur - Fondation Cenci Bolognetti, Università degli Studi di Roma 'La Sapienza' [Rome] - Faculty of Pharmacy & Medicine, Università degli Studi di Roma 'La Sapienza' [Rome] - Faculty of Pharmacy and Medicine, Università degli Studi di Roma 'La Sapienza' [Rome] |
| المصدر: | BBA-Biochimica et Biophysica Acta BBA-Biochimica et Biophysica Acta, Elsevier, 2014, 1839 (9), pp.813-25. ⟨10.1016/j.bbagrm.2014.06.017⟩ BBA-Biochimica et Biophysica Acta, Elsevier, 2014, 1839 (9), pp.813-25. <10.1016/j.bbagrm.2014.06.017> |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Biochemistry, Cancer testis antigen, Epigenesis, Genetic, MESH: DNA Methylation, 0302 clinical medicine, Structural Biology, Histone methylation, MESH: Epigenesis, Genetic, Cancer epigenetics, Promoter Regions, Genetic, Receptor, Notch3, Cells, Cultured, Epigenomics, 0303 health sciences, Receptors, Notch, MESH: Gene Expression Regulation, Neoplastic, Chromatin, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, DNA/histone methylation, MESH: Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, 030220 oncology & carcinogenesis, DNA methylation, MESH: Cells, Cultured, Biophysics, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Chromatin remodeling, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH: Promoter Regions, Genetic, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Epigenetics, Settore BIO/10, Molecular Biology, Oncogene, 030304 developmental biology, MESH: Humans, DNA Methylation, T cell acute lymphoblastic leukemia, t cell acute lymphoblastic leukemia, cancer testis antigen, dna/histone methylation, oncogene, chromatin, Cancer cell, Cancer research, MESH: Receptors, Notch, MESH: DNA-Binding Proteins |
| الوصف: | International audience; Aberrant upregulation of NOTCH3 gene plays a critical role in cancer pathogenesis. However, the underlying mechanisms are still unknown. We tested here the hypothesis that aberrant epigenetic modifications in the NOTCH3 promoter region might account for its upregulation in cancer cells. We compared DNA and histone methylation status of NOTCH3 promoter region in human normal blood cells and T cell acute lymphoblastic leukemia (T-ALL) cell lines, differentially expressing NOTCH3. We found that histone methylation, rather than DNA hypomethylation, contributes towards establishing an active chromatin status of NOTCH3 promoter in NOTCH3 overexpressing cancer cells. We discovered that the chromatin regulator protein BORIS/CTCFL plays an important role in regulating NOTCH3 gene expression. We observed that BORIS is present in T-ALL cell lines as well as in cell lines derived from several solid tumors overexpressing NOTCH3. Moreover, BORIS targets NOTCH3 promoter in cancer cells and it is able to induce and to maintain a permissive/active chromatin conformation. Importantly, the association between NOTCH3 overexpression and BORIS presence was confirmed in primary T-ALL samples from patients at the onset of the disease. Overall, our results provide novel insights into the determinants of NOTCH3 overexpression in cancer cells, by revealing a key role for BORIS as the main mediator of transcriptional deregulation of NOTCH3. |
| اللغة: | English |
| تدمد: | 0006-3002 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::128d8b42867692abc79b67385f4f8aa8Test http://hdl.handle.net/2108/291556Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....128d8b42867692abc79b67385f4f8aa8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00063002 |
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