Landi, Rosaria (2014) DNA methylation/ demethylation cycles in Estrogen induced transcription. [Tesi di dottorato]

Anteprima

Testo Landi_Rosaria_26.pdf Download (8MB) | Anteprima

Abstract

Genomic DNA can be covalently modified by methylation, which is layered on the primary genetic information and alters gene expression. There are two patterns of DNA methylation. The first, stable methylation, seen in imprinting, is inherited in a sex-specific fashion and is invariant among individuals and cell types. Unstable or metastable methylation is variable among individuals and cell types and is associated with cancer and aging. The primary cause of somatic DNA methylation is not known. Here we show that DNA methylation is linked with transcription and repair. The effectors of DNA methylation are DNA methyltransferases (DNMTs) that catalyze either de novo or maintenance methylation of hemimethylated DNA during replication. Demethylation of DNA has recently been linked to BER enzymes, which remove mismatched or alkylated bases. CpG de-methylation is also associated with mC oxidation and marks transcription start sites (Zhu 2009; Chen and Riggs 2011) . The aim of my study is to analyze the association between DNA methylation and Estrogen-dependent induction of transcription. The estrogens are hormones that bound to the receptors penetrate into chromatin-DNA and bind specific DNA sequence present in several sites in the genome. The active receptors bound to DNA, trigger oxidative demethylation of histones locally and induce DNA (G) oxidation (Perillo et al. 2008). Simultaneously, on the same sites DNMT1, 3a, DNA methyltransferase enzymes, are recruited and stimulate a wave of methylation of CpGs. Methylated CpGs and oxidized Gs in the target sites during transcription initiation accumulate and are processed by BER and NER enzymes.

Downloads

Actions (login required)

Modifica documento