Obesity related methylation changes in DNA of peripheral blood leukocytes
BMC MEDICINE
Authors: Wang, Xiaoling; Zhu, Haidong; Snieder, Harold; Su, Shaoyong; Munn, David; Harshfield, Gregory; Maria, Bernard L.; Dong, Yanbin; Treiber, Frank; Gutin, Bernard; Shi, Huidong
Abstract
Background: Despite evidence linking obesity to impaired immune function, little is known about the specific mechanisms. Because of emerging evidence that immune responses are epigenetically regulated, we hypothesized that DNA methylation changes are involved in obesity induced immune dysfunction and aimed to identify these changes. Method: We conducted a genome wide methylation analysis on seven obese cases and seven lean controls aged 14 to 18 years from extreme ends of the obesity distribution and performed further validation of six CpG sites from six genes in 46 obese cases and 46 lean controls aged 14 to 30 years. Results: In comparison with the lean controls, we observed one CpG site in the UBASH3A gene showing higher methylation levels and one CpG site in the TRIM3 gene showing lower methylation levels in the obese cases in both the genome wide step ( P = 5 x 10(-6) and P = 2 x 10(-5) for the UBASH3A and the TRIM3 gene respectively) and the validation step ( P = 0.008 and P = 0.001 for the UBASH3A and the TRIM3 gene respectively). Conclusions: Our results provide evidence that obesity is associated with methylation changes in blood leukocyte DNA. Further studies are warranted to determine the causal direction of this relationship as well as whether such methylation changes can lead to immune dysfunction. See commentary: http://www.biomedcentral.com/1741-7015/8/XX/abstract
Emerging RNA-binding roles in the TRIM family of ubiquitin ligases
BIOLOGICAL CHEMISTRY
Authors: Williams, Felix Preston; Haubrich, Kevin; Perez-Borrajero, Cecilia; Hennig, Janosch
Abstract
TRIM proteins constitute a large, diverse and ancient protein family which play a key role in processes including cellular differentiation, autophagy, apoptosis, DNA repair, and tumour suppression. Mostly known and studied through the lens of their ubiquitination activity as E3 ligases, it has recently emerged that many of these proteins are involved in direct RNA binding through their NHL or PRY/SPRY domains. We summarise the current knowledge concerning the mechanism of RNA binding by TRIM proteins and its biological role. We discuss how RNA-binding relates to their previously described functions such as E3 ubiquitin ligase activity, and we will consider the potential role of enrichment in membrane-less organelles.