DNA methylation, chromatin inheritance, and cancer

Citation
Mr. Rountree et al., DNA methylation, chromatin inheritance, and cancer, ONCOGENE, 20(24), 2001, pp. 3156-3165
Citations number
107
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
ONCOGENE
ISSN journal
0950-9232 → ACNP
Volume
20
Issue
24
Year of publication
2001
Pages
3156 - 3165
Database
ISI
SICI code
0950-9232(20010528)20:24<3156:DMCIAC>2.0.ZU;2-#
Abstract
Cancer is a process driven by the accumulation of abnormalities in gene fun ction. While many of these changes are genetic, epigenetically mediated cha nges in gene expression are being increasingly appreciated. This latter pro cess emphasizes the need to understand two key components of heritable, but reversible, modulation of gene promoter function that are closely tied to one another - formation of chromatin which modulates transcription and esta blishing patterns of DNA methylation, The link lies first in the recruitmen t to methylated cytosines of a family of methyl-CpG binding domain proteins (MBDs), which are direct transcriptional repressors and can complex with t ranscriptional core-pressors including histone deacetylases (HDACs), Additi onally, the proteins that catalyze DNA methylation, DNA methyltransferases (DNMTs), also directly repress transcription and associate with HDACs. Regu lation of these above chromatin-DNA methylation interactions as a function of DNA replication timing is emerging as a key event in the inheritance of transcriptionally repressed domains of the genome. Importantly, synergy bet ween HDAC activity and DNA methylation is operative for a key epigenetic ab normality in cancer cells, transcriptional silencing of tumor suppressor ge nes. This change has now been recognized for genes that are essential for n ormal regulation of virtually every major cell function including cell grow th, differentiation, apoptosis, DNA repair, and cell-cell, cell-substratum interaction. Understanding the molecular determinants of both normal and ab normal patterns of chromatin formation and DNA methylation thus holds great promise for our understanding of cancer and for means to better diagnose, prevent, and treat this means to better disease.