Readers of DNA methylation, the MBD family as potential therapeutic targets
| Autor: | David C. Williams, Gordon D. Ginder |
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| Rok vydání: | 2018 |
| Předmět: |
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Molecular 0301 basic medicine Pharmacology Regulation of gene expression Methylation DNA Methylation Biology DNA-binding protein Chromatin DNA-Binding Proteins 03 medical and health sciences 030104 developmental biology Neoplasms DNA methylation Cancer research Animals Humans Gene silencing Pharmacology (medical) Molecular Targeted Therapy Epigenetics Gene |
| Zdroj: | Pharmacology & Therapeutics. 184:98-111 |
| ISSN: | 0163-7258 |
| Popis: | DNA methylation represents a fundamental epigenetic modification that regulates chromatin architecture and gene transcription. Many diseases, including cancer, show aberrant methylation patterns that contribute to the disease phenotype. DNA methylation inhibitors have been used to block methylation dependent gene silencing to treat hematopoietic neoplasms and to restore expression of developmentally silenced genes. However, these inhibitors disrupt methylation globally and show significant off-target toxicities. As an alternative approach, we have been studying readers of DNA methylation, the 5-methylcytosine binding domain family of proteins, as potential therapeutic targets to restore expression of aberrantly and developmentally methylated and silenced genes. In this review, we discuss the role of DNA methylation in gene regulation and cancer development, the structure and function of the 5-methylcytosine binding domain family of proteins, and the possibility of targeting the complexes these proteins form to treat human disease. |
| Databáze: | OpenAIRE |
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