Epigenetic changes

Due to their functional involvement in specific molecular pathways, miRNAs have become interesting targets for therapeutic intervention. Examples of disease-related mechanisms affected by miRNAs include single-nucleotide polymorphisms (SNPs) in 3 UTR sequences (23, 24) or in miRNA genes (25, 26) that may affect normal protein expression and has been identified in association with heart failure (27) and cancer (25, 28). Chromosomal deletions and epigenetic changes involving miRNA also cause abnormal protein expression that is associated with malfunctions... 

A current hypothesis is that in utero exposure to diethylstilbestrol leads to genetic or epigenetic changes in the primordial oocytes that are formed in the first trimester of gestation in the daughter. These changes can then be inherited by grandchildren. 

The analysis of epigenetic changes, mainly the covalent addition of methyl groups to the 5 position of Cytosine in CpG sequences, has become an increasingly important field in genetic research. The DNA methylation has... 

Kondo Y, Issa JP. Epigenetic changes in colorectal cancer. Cancer Metastasis Rev 2004 23 29-39. 

Kalebic T. Epigenetic changes potential therapeutic targets. Ann NY Acad Sci 2003 983 278-285. 

Decitabine (1) is a hypomethylating agent that exhibits potent antileukemic activity by inducing epigenetic changes in chromatin or reactivating tumor suppressor genes. It is administered intravenously at 15 mg/m2 over 3 h every 8 h for 3 consecutive days. The frequency of this administration is every 6 weeks. 

Here Nm is the expected number of initiated cells during a time step At, N is the normal hepatocyte number density, and is the mutation probability per cell division. In this case mutation refers to any genetic or epigenetic change that leads to GST-P (glutathione 5-transferase placental form) expression in the liver cells. 

There is increasing evidence suggesting that epigenetic changes in gene expression underlie neurodegeneration and CNS disorders... 

---