MeCP2: a trip from a chromatin protein to neurological disorders

MeCP2 belongs to the large family of intrinsically disordered proteins (IDPs). It is universally expressed in all tissues and hence plays an important role in many of the diseases that involve dysregulated DNA methylation. Mutations in MeCP2 cause neurodevelopmental alterations that account for more than 95% of Rett syndrome cases. The presence of one molecule of MeCP2 for every two nucleosomes in neuronal chromatin suggests that alterations of this protein http://www.selleckchem.com " title="kinase inhibitor">kinase inhibitormay be involved in many processes.

Ubiquitination targeting the protein lead to rapid degradation by the 26S ubiquitin proteasome system (UPS). Studies showed that MeCP2 has a higher preference for binding methylated DNA, especially in the presence of competitor DNA, a situation similar to that found in the nucleus.

A potential insight into the chromatin conformation of such MeCP2-rich chromatin may be gained from the accumulation of this protein during neuronal development. The transitionhttp://www.selleckchem.com " title="selleck chemicals">selleck chemicals from 5mC to 5hmC increases during neuronal differentiation and brain development and during aging.

MeCP2 plays an important role in cancer, in connection with its binding to methylated promoter CpG islands of tumor suppressor genes. There is a need to further explore the role of MeCP2 in connection with all these diseases, especially as it pertains to the different aspects of its involvement at the molecular level.

Ovarian cancer is the most lethal gynaecological cancer, which accounts for about 3% of cancers among women, but causes more deaths than any other cancer of the female reproductive system. At present, the primary treatment is cytoreductive surgery and chemotherapy, such as docetaxeland paclitaxel. Also, more molecularly targeted therapies are being developed in ovarian cancer. In order to reduce the majority relapse, it is necessary to identify biological markers of response and survival, measurable at presentation.

Some evidences demonstrates that epigenetic variability, such as DNA methylation, at candidate loci in peripheral blood DNA may be useful as biomarkers of breast cancer risk, which may predicts clinical outcomes following chemotherapy. In a recent clinical study in white blood cells by Flanagan et al, mean stratifin (SFN) methylation associated with progression-free survival (PFS) is identified in the paclitaxel arm of the trial.

Though it is still necessary to be validated in further independent clinical studies, the existing result indicates that DNA methylation status associating with markers of toxicity may identify those patients at risk of toxicity to paclitaxel or docetaxel. Targeted therapy is given based on the patient’s condition, which undoubtedly provides significant benefits for the treatment of patients suffering from Ovarian Cancer.