Epigenetics, first described by Conrad Waddington, defines how pathways setting a specific pheno-type and heritable cellular functions are activated in a DNA independent way. Epigenetics concerns the study of genome structure and accessibility that regulates patterns of gene expression through the dynamic compaction and opening the chromatin structure. Vincent Allfrey profetically declared in 1964 that histone modifications could influence gene expression. In cancer very often cells show a profound modification of DNA methylation and mutations in chromatin regulators. These evidences provided therefore a clear link between epigenetics and neoplasia. Advanced molecular technology such as Deep-sequencing and ChIP-Seq revealed the frequent re-localization in cancer of many PTM readers such the Ac-Lys binding bromodomain. These results were important for the development of novel classes of epigenetic drugs some of which are inhibitors of histone modifyers or molecule interacting with reader domains. Since cancer imply profound changes in the epigenetic profile and in gene transcription a future challenge of molecular and chemical biology will be to develop novel epigenetic compounds able to correct the epigenetic disfunction and, possibly, coadiuvate canonical therapy in the cure of cancer.
Epigenetica: Un nuovo strumento per la diagnosi e il trattamento dei tumori
Filetici;Patrizia
2015
Abstract
Epigenetics, first described by Conrad Waddington, defines how pathways setting a specific pheno-type and heritable cellular functions are activated in a DNA independent way. Epigenetics concerns the study of genome structure and accessibility that regulates patterns of gene expression through the dynamic compaction and opening the chromatin structure. Vincent Allfrey profetically declared in 1964 that histone modifications could influence gene expression. In cancer very often cells show a profound modification of DNA methylation and mutations in chromatin regulators. These evidences provided therefore a clear link between epigenetics and neoplasia. Advanced molecular technology such as Deep-sequencing and ChIP-Seq revealed the frequent re-localization in cancer of many PTM readers such the Ac-Lys binding bromodomain. These results were important for the development of novel classes of epigenetic drugs some of which are inhibitors of histone modifyers or molecule interacting with reader domains. Since cancer imply profound changes in the epigenetic profile and in gene transcription a future challenge of molecular and chemical biology will be to develop novel epigenetic compounds able to correct the epigenetic disfunction and, possibly, coadiuvate canonical therapy in the cure of cancer.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
