Roles of Wnt Signaling Pathway and ROR2 Receptor in Embryonic Development: An Update Review Article

Epigenetics Insights

article

Carol Bernstein¹ 

[1] Department of Cellular and Molecular Medicine, University of Arizona

关键词: DNA methylation;    memory;    DNA demethylation;    TET enzymes;    DNA methyltransferase (DNMT);    early growth response gene 1 (EGR1);    immediate early gene (IEG);    8-oxoguanine glycosylase (OGG1);    long-term memory;    topoisomerase II beta;    hippocampus;    cortex;    neuron;   

DOI  :  10.1177/25168657211072499

学科分类：兽医学

来源: Tu Delft Transport Institute

【 摘 要 】

A single event can cause a life-long memory. Memories physically reside in neurons, and changes in neuronal gene expression are considered to be central to memory. Early models proposed that specific DNA methylations of cytosines in neuronal DNA encode memories in a stable biochemical form. This review describes recent research that elucidates the molecular mechanisms used by the mammalian brain to form DNA methylcytosine encoded memories. For example, neuron activation initiates cytosine demethylation by stimulating DNA topoisomerase II beta (TOP2B) protein to make a temporary DNA double-strand break (repaired within about 2 hours) at a promoter of an immediate early gene, EGR1 , allowing expression of this gene. The EGR1 proteins then recruit methylcytosine dioxygenase TET1 proteins to initiate demethylation at several hundred genes, facilitating expression of those genes. Initiation of demethylation of cytosine also occurs when OGG1 localizes at oxidized guanine in a methylated CpG site and recruits TET1 for initiation of demethylation at that site. DNMT3A2 is another immediate early gene upregulated by synaptic activity. DNMT3A2 protein catalyzes de novo DNA methylations. These several mechanisms convert external experiences into DNA methylations and initiated demethylations of neuronal DNA cytosines, causing changes in gene expression that are the basis of long-term memories.

【 授权许可】

CC BY|CC BY-NC