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Discusses research made towards understanding the molecular mechanism of CGG repeat expansion and physiological functions of fragile X mental retardation-1 protein (FRMP) in patients with fragile X syndrome. Implication of the protein in protein translation as it is found associated with polyribosomes and the rough endoplasmic reticulum; Instability and methylation of CGG repeats.

DNA methylation is a class of epigenetic modification essential for coordinating gene expression timing and magnitude throughout normal brain development and for proper brain function following development. Aberrant methylation changes are associated with changes in chromatin architecture, transcriptional alterations and a host of neurological disorders and diseases. This review highlights recent advances in our understanding of the methylome's functionality and covers potential new roles for DNA methylation, their readers, writers, and erasers. Additionally, we examine novel insights into the relationship between the methylome, DNA-protein interactions, and their contribution to neurodegenerative diseases. Lastly, we outline the gaps in our knowledge that will likely be filled through the widespread use of newer technologies that provide greater resolution into how individual cell types are affected by disease and the contribution of each individual modification site to disease pathogenicity., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Preeclampsia and gestational diabetes mellitus (GDM) are the most common clinical conditions in pregnancy that could result in adverse in utero environments. Fetal exposure to poor environments may raise the long-term risk of postnatal disorders, while epigenetic modifications could be involved. Recent research has implicated involvement of 5-hydroxymethylcytosine (5hmC), a DNA base derived from 5-methylcytosine, via oxidation by ten-eleven translocation (TET) enzymes, in DNA methylation-related plasticity. Here, we show that the TET2 expression and 5hmC abundance are significantly altered in the umbilical veins of GDM and preeclampsia. Genome-wide profiling of 5hmC revealed its specific reduction on intragenic regions from both GDM and preeclampsia compared to healthy controls. Gene Ontology analysis using loci bearing unique GDM- and preeclampsia-specific loss-of-5hmC indicated its impact on several critical biological pathways. Interestingly, the substantial alteration of 5hmC on several transposons and repetitive elements led to their differential expression. The alteration of TET expression, 5hmC levels and 5hmC-mediated transposon activity was further confirmed using established hypoxia cell culture model, which could be rescued by vitamin C, a known activator of TET proteins. Together, these results suggest that adverse pregnancy environments could influence 5hmC-mediated epigenetic profile and contribute to abnormal development of fetal vascular systems that may lead to postnatal diseases., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Branched chain amino acids (BCAAs) play critical roles in cell and tissue functions in addition to being important components of protein structure. The multifunctional roles speak to the need for maintaining tight control of their concentration within cells. As the BCAA cannot be made de novo in mammals, their cellular concentration is a function of dietary intake, endogenous protein turnover and catabolism of the three amino acids. The branched chain alpha-ketoacid dehydrogenase (BCKD) complex commits the BCAA to degradation and thus is vital in controlling their concentration within a cell. In mammals, BCKD activity state depends on the presence of a covalently bound phosphate on one protein component of the complex. Phosphate is added to the protein through the action of the complex-specific kinase and results in BCKD inactivation. Here, we demonstrate that another reaction plays a role in determining the total amount of BCKD present in a cell. The microRNA (miR29b) molecule tested is targeted to the mRNA for the dihydrolipoamide branched chain acyltransferase component of BCKD and prevents translation when bound. This is the first demonstration of the use of a microRNA to exert control on a metabolic pathway of amino acid catabolism in mammals and offers an explanation for the observed differences in the amount of the BCKD complex present in different tissues and under varying nutritional states.