REVIEW

Cell Research, 15(9):679-690, September 2005

Dynamic and reversibility of heterochromatic gene silencing in human disease

Giuseppe ZARDO^1,2, Francesco FAZI^2,3, Lorena TRAVAGLINI^2,3, Clara NERVI^2,3,*

¹Departments of Cellular Biotechnology and Hematology, University of Rome "La Sapienza", Via di Castel Romano 100, Rome 00128, Italy
²San Raffaele Bio-medical Science Park of Rome, Via di Castel Romano 100, Rome 00128, Italy
³Departments of Histology and Medical Embryology, University of Rome "La Sapienza", Via di Castel Romano 100, Rome 00128, Italy

Correspondence: Clara NERVI +39-06-80319049/52 (phone) +39-06-80319054 (fax) clara.nervi@uniroma1.it

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In eukaryotic organisms cellular fate and tissue specific gene expression are regulated by the activity of proteins known as transcription factors that by interacting with specific DNA sequences direct the activation or repression of target genes. The post genomic era has shown that transcription factors are not the unique key regulators of gene expression. Epigenetic mechanisms such as DNA methylation, post-translational modifications of histone proteins, remodeling of nucleosomes and expression of small regulatory RNAs also contribute to regulation of gene expression, determination of cell and tissue specificity and assurance of inheritance of gene expression levels. The relevant contribution of epigenetic mechanisms to a proper cellular function is highlighted by the effects of their deregulation that cooperate with genetic alterations to the development of various diseases and to the establishment and progression of tumors.

Keywords: DNA methylation, chromatin remodeling, epigenetics, retinoic acid, acute myeloid leukemia.