Mammalian Epigenetic Mechanisms

The mammalian genome is packaged into chromatin that is further compacted into three-dimensional structures consisting of distinct functional domains. The higher order structure of chromatin is in part dictated by enzymatic DNA methylation and histone modifications to establish epigenetic layers controlling gene expression and cellular functions, without altering the underlying DNA sequences. Apart from DNA and histone modifications, non-coding RNAs can also regulate the dynamics of the mammalian gene expression and various physiological functions including cell division, differentiation, and apoptosis. Aberrant epigenetic signatures are associated with abnormal developmental processes and diseases such as cancer. In this review, we will discuss the different layers of epigenetic regulation, including writer enzymes for DNA methylation, histone modifications, non-coding RNA, and chromatin conformation. We will highlight the combinatorial role of these structural and chemical modifications along with their partners in various cellular processes in mammalian cells. We will also address the cis and trans interacting reader proteins that recognize these modifications and eraser enzymes that remove these marks. Furthermore, an attempt will be made to discuss the interplay between various epigenetic writers, readers, and erasures in the establishment of mammalian epigenetic mechanisms. (c) 2014 IUBMB Life, 66(4):240-256, 2014