Development-linked Differences in Cytosine 5-Hydroxymethylation in Mammalian DNA: Relationship to 5-Methylcytosine and Function
Melanie Ehrlich, Michelle Lacey, Guoqiang Zhang, Kenneth C. Ehrlich and Sriharsa Pradhan
from: Epigenetics: Current Research and Emerging Trends (Edited by: Brian P. Chadwick). Caister Academic Press, U.K. (2015) Pages: 77-104.
Abstract
There has been a burst of research activity since the recent definitive determination of 5-hydroxymethylcytosine (5hmC) as a differentiation-linked base in mammalian DNA. Differences in 5hmC tissue-specificity are even more striking than those for 5-methylcytosine (5mC), the DNA base from which 5hmC is derived. There are strong associations of 5hmC with extended promoter regions but its distribution around transcription start sites is different depending on the genes' transcriptional activity. The levels of 5hmC in the body of genes and in weak or strong enhancer-type chromatin partly correlate with transcription levels. We summarize some of the frequently used methods for analyzing 5hmC genomic profiles and recent evidence for correlations of genomic 5hmC with major histone modifications, differential splicing, differentiation, disease, and DNA demethylation. In addition, we compare DNA hydroxymethylation and DNA methylation in embryonic stem cells and the neural and skeletal muscle lineages as well as the distinct enrichment patterns of these two modifications along the genome. Because evidence indicates that 5hmC functions as both an intermediate in DNA demethylation and as a stable component of DNA with many different features from those of 5mC, 5hmC probably has a wide variety of roles in differentiation and sometimes in cell physiology read more ...
