Preventing transcriptional gene silencing by active DNA demethylation

• Published in: FEBS letters Vol. 579; no. 26; pp. 5889 - 5898
• Main Authors: Kapoor, Avnish, Agius, Fernanda, Zhu, Jian-Kang
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 31-10-2005
• Subjects: Amino Acid Sequence; Arabidopsis; Arabidopsis - genetics; Arabidopsis Proteins - metabolism; Arabidopsis Proteins - physiology; Chromatin - chemistry; DNA - chemistry; DNA demethylation; DNA glycosylase; DNA Glycosylases - chemistry; DNA Glycosylases - metabolism; DNA Methylation; DNA Repair; Gene Silencing; Genome; Genome, Plant; Heterochromatin - chemistry; Models, Chemical; Molecular Sequence Data; Mutation; Nuclear Proteins - metabolism; Nuclear Proteins - physiology; Protein Structure, Tertiary; Recombinant Proteins - chemistry; RNA, Small Interfering - metabolism; ROS1; Transcription, Genetic; Transcriptional gene silencing; DNA methylation; DNA demethylation; DNA glycosylase; Transcriptional gene silencing; Arabidopsis; ROS1
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2005.08.039

DNA methylation is important for stable transcriptional gene silencing. DNA methyltransferases for de novo as well as maintenance methylation have been well characterized. However, enzymes responsible for active DNA demethylation have been elusive and several reported mechanisms of active demethylation have been controversial. There has been a critical need for genetic analysis in order to firmly establish an in vivo role for putative DNA demethylases. Mutations in the bifunctional DNA glycosylase/lyase ROS1 in
Arabidopsis cause DNA hypermethylation and transcriptional silencing of specific genes. Recombinant ROS1 protein has DNA glycosylase/lyase activity on methylated but not unmethylated DNA substrates. Therefore, there is now strong genetic evidence supporting a base excision repair mechanism for active DNA demethylation. DNA demethylases may be critical factors for genome wide hypomethylation seen in cancers and possibly important for epigenetic reprogramming during somatic cell cloning and stem cell function.