The Identification of Mammalian Proteins Involved in Epigenetics
Luke Isbel, Harry Oey and Emma Whitelaw
from: Epigenetics: Current Research and Emerging Trends (Edited by: Brian P. Chadwick). Caister Academic Press, U.K. (2015) Pages: 105-124.
Abstract
Mutagenesis screening in Drosophila has identified genes involved in epigenetic processes and in most cases the mammalian homologues have been found to have similar functions. However, there are some gene silencing mechanisms that are present in mammals but absent in Drosophila, such as DNA methylation. So mutagenesis screens have also been carried out in the mouse and some novel genes have been found. Random mutagenesis screens in the mouse require a massive effort but they do facilitate the study of the phenotypic consequences of haploinsufficiency and this is providing us with clear associations between epigenetic dysfunction and human disease. In vitro RNAi screening in cell lines provides a high throughput alternative but faces some difficulties, in particular off- target effects. Biochemical approaches such as affinity pull down and mass spectrometry have provided researchers with a means to identify binding partners. Here we review the efforts made to identify the mammalian complexes necessary for epigenetic events. While the set of proteins found to be involved is now extensive, the challenge is to understand how they work together to achieve the highly regulated patterns of gene expression seen in the adult organism read more ...
