A Novel Mechanism for CTCF in the Epigenetic Regulation of Bax in Breast Cancer Cells
We previously reported the association of elevated levels of the multifunctional transcription factor, CCCTC binding factor (CTCF), in breast cancer cells with the specific anti-apoptotic function of CTCF. To understand the molecular mechanisms of this phenomenon, we investigated regulation of the h...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2013-08-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558613800954 |
| _version_ | 1811278730198253568 |
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| author | Claudia Fabiola Méndez-Catalá Svetlana Gretton Alexander Vostrov Elena Pugacheva Dawn Farrar Yoko Ito France Docquier Georgia-Xanthi Kita Adele Murrell Victor Lobanenkov Elena Klenova |
| author_facet | Claudia Fabiola Méndez-Catalá Svetlana Gretton Alexander Vostrov Elena Pugacheva Dawn Farrar Yoko Ito France Docquier Georgia-Xanthi Kita Adele Murrell Victor Lobanenkov Elena Klenova |
| author_sort | Claudia Fabiola Méndez-Catalá |
| collection | DOAJ |
| description | We previously reported the association of elevated levels of the multifunctional transcription factor, CCCTC binding factor (CTCF), in breast cancer cells with the specific anti-apoptotic function of CTCF. To understand the molecular mechanisms of this phenomenon, we investigated regulation of the human Bax gene by CTCF in breast and non-breast cells. Two CTCF binding sites (CTSs) within the Bax promoter were identified. In all cells, breast and non-breast, active histone modifications were present at these CTSs, DNA harboring this region was unmethylated, and levels of Bax mRNA and protein were similar. Nevertheless, up-regulation of Bax mRNA and protein and apoptotic cell death were observed only in breast cancer cells depleted of CTCF. We proposed that increased CTCF binding to the Bax promoter in breast cancer cells, by comparison with non-breast cells, may be mechanistically linked to the specific apoptotic phenotype in CTCF-depleted breast cancer cells. In this study, we show that CTCF binding was enriched at the Bax CTSs in breast cancer cells and tumors; in contrast, binding of other transcription factors (SP1, WT1, EGR1, and c-Myc) was generally increased in non-breast cells and normal breast tissues. Our findings suggest a novel mechanism for CTCF in the epigenetic regulation of Bax in breast cancer cells, whereby elevated levels of CTCF support preferential binding of CTCF to the Bax CTSs. In this context, CTCF functions as a transcriptional repressor counteracting influences of positive regulatory factors; depletion of breast cancer cells from CTCF therefore results in the activation of Bax and apoptosis. |
| first_indexed | 2024-04-13T00:41:13Z |
| format | Article |
| id | doaj.art-6883d1ee252447018b12ab996362d123 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-04-13T00:41:13Z |
| publishDate | 2013-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-6883d1ee252447018b12ab996362d1232022-12-22T03:10:09ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022013-08-0115889891210.1593/neo.121948A Novel Mechanism for CTCF in the Epigenetic Regulation of Bax in Breast Cancer CellsClaudia Fabiola Méndez-Catalá0Svetlana Gretton1Alexander Vostrov2Elena Pugacheva3Dawn Farrar4Yoko Ito5France Docquier6Georgia-Xanthi Kita7Adele Murrell8Victor Lobanenkov9Elena Klenova10School of Biological Sciences, University of Essex, Colchester, Essex, United KingdomSchool of Biological Sciences, University of Essex, Colchester, Essex, United KingdomMolecular Pathology Section, Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MDMolecular Pathology Section, Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MDSchool of Biological Sciences, University of Essex, Colchester, Essex, United KingdomCancer Research UK Cambridge Research Institute, Cambridge, United KingdomHelen Rollason Research Laboratory, PMI 208, Postgraduate Medical Institute (PMI), Anglia Ruskin University, Chelmsford, Essex, United KingdomSchool of Biological Sciences, University of Essex, Colchester, Essex, United KingdomCancer Research UK Cambridge Research Institute, Cambridge, United KingdomMolecular Pathology Section, Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MDSchool of Biological Sciences, University of Essex, Colchester, Essex, United KingdomWe previously reported the association of elevated levels of the multifunctional transcription factor, CCCTC binding factor (CTCF), in breast cancer cells with the specific anti-apoptotic function of CTCF. To understand the molecular mechanisms of this phenomenon, we investigated regulation of the human Bax gene by CTCF in breast and non-breast cells. Two CTCF binding sites (CTSs) within the Bax promoter were identified. In all cells, breast and non-breast, active histone modifications were present at these CTSs, DNA harboring this region was unmethylated, and levels of Bax mRNA and protein were similar. Nevertheless, up-regulation of Bax mRNA and protein and apoptotic cell death were observed only in breast cancer cells depleted of CTCF. We proposed that increased CTCF binding to the Bax promoter in breast cancer cells, by comparison with non-breast cells, may be mechanistically linked to the specific apoptotic phenotype in CTCF-depleted breast cancer cells. In this study, we show that CTCF binding was enriched at the Bax CTSs in breast cancer cells and tumors; in contrast, binding of other transcription factors (SP1, WT1, EGR1, and c-Myc) was generally increased in non-breast cells and normal breast tissues. Our findings suggest a novel mechanism for CTCF in the epigenetic regulation of Bax in breast cancer cells, whereby elevated levels of CTCF support preferential binding of CTCF to the Bax CTSs. In this context, CTCF functions as a transcriptional repressor counteracting influences of positive regulatory factors; depletion of breast cancer cells from CTCF therefore results in the activation of Bax and apoptosis.http://www.sciencedirect.com/science/article/pii/S1476558613800954 |
| spellingShingle | Claudia Fabiola Méndez-Catalá Svetlana Gretton Alexander Vostrov Elena Pugacheva Dawn Farrar Yoko Ito France Docquier Georgia-Xanthi Kita Adele Murrell Victor Lobanenkov Elena Klenova A Novel Mechanism for CTCF in the Epigenetic Regulation of Bax in Breast Cancer Cells Neoplasia: An International Journal for Oncology Research |
| title | A Novel Mechanism for CTCF in the Epigenetic Regulation of Bax in Breast Cancer Cells |
| title_full | A Novel Mechanism for CTCF in the Epigenetic Regulation of Bax in Breast Cancer Cells |
| title_fullStr | A Novel Mechanism for CTCF in the Epigenetic Regulation of Bax in Breast Cancer Cells |
| title_full_unstemmed | A Novel Mechanism for CTCF in the Epigenetic Regulation of Bax in Breast Cancer Cells |
| title_short | A Novel Mechanism for CTCF in the Epigenetic Regulation of Bax in Breast Cancer Cells |
| title_sort | novel mechanism for ctcf in the epigenetic regulation of bax in breast cancer cells |
| url | http://www.sciencedirect.com/science/article/pii/S1476558613800954 |
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