Gsk 3 Regulates Dna Methylation - 1046 Words

Gsk-3 Regulates DNA Methylation Gsk-3 activity has been observed to regulate DNA methylation through altered expression of DNA methyltransferase Dnmt3a2. This was confirmed by knocking out both Gsk-3 isoforms (Gsk-3 DKO) in mouse ESCs, resulting in the reduction of DNA methylation and altered gene expression (Meredith et al., 2015; Popkie et al., 2010). Lithium mimics this reduced Gsk-3 activity in two ways: direct inhibition and indirect inhibition by increasing inhibitory phosphorylation of Gsk-3 (Jope, 2003). These two effects work in synergy to influence Gsk-3 regulated functions. Interestingly, lithium is commonly used as a mood stabilizer treatment for patients with bipolar disorder (BPD) (Phiel, 2001). The exact mechanism behind how†¦show more content†¦Methyl-seq was performed on genomic DNA isolated from lymphoblasts, providing DNA methylation patterns of the entire genome for each individual. Several loci displayed hypermethylation in both BPD patients compared to their unaffected siblings. When the lymphoblast cells were treated with a therapeutic dose of lithium (1mM), results showed hypomethylation at several loci. Among these, one locus had been hypermethylated in the BPD cells. This differentially methylated locus was where the novel lncRNA, LINC00486, was located. Sequencing data has indicated LINC00486 is found in human chromosome 2 and is flanked by genes TTC27 and LTBP1. A mouse homolog has yet to be discovered. Three distinct RNAs are predicted to be transcribed from the LINC00486 locus, each of different lengths and containing different exons. Non-Coding RNA Overview Recent advantages in genome-wide analyses have revealed that roughly 90% of the human genome is transcribed, yet less than 3% of the genome consists of protein-coding genes (Wu et al., 2013). The remaining genes are transcribed as noncoding RNAs (ncRNAs), which resemble mRNA in length and splicing structures yet do not encode any proteins (Wu et al., 2013). It has been debated whether all of the ncRNA transcripts are functional due to their low expression levels and low evolutionary conservation. However, many functional ncRNA have