Abstract
Epigenetic changes caused by DNA methylation and histone modifications play important roles in the regulation of various cellular processes and development. Recent discoveries of 5-methylcytosine (5mC) oxidation derivatives including 5-hydroxymethylcytosine (5hmC), 5-formylcytsine (5fC) and 5-carboxycytosine (5caC) in mammalian genome further expand our understanding of the epigenetic regulation. Analysis of DNA modification patterns relies increasingly on sequencing-based profiling methods. A number of different approaches have been established to map the DNA epigenomes with single-base resolution, as represented by the bisulfite-based methods, such as classical bisulfite sequencing (BS-seq), TAB-seq (TET-assisted bisulfite sequencing), oxBS-seq (oxidative bisulfite sequencing) and etc. These methods have been used to generate base-resolution maps of 5mC and its oxidation derivatives in genomic samples. The focus of this review will be to discuss the chemical methodologies that have been developed to detect the cytosine derivatives in the genomic DNA.
Highlights
The term “Epigenetics” was coined by the British developmental biologist Conrad Waddington in 1939 (Waddington, 1939), and can be defined as heritable changes in traits that occur without alteration of the underlying primary DNA sequence
Bisulfite conversion of genomic DNA combined with next-generation sequencing (BS-seq), which has been regarded as the golden standard for 5mC detection, is widely used to study genome-wide DNA methylation dynamics with single-base resolution (Lister and Ecker, 2009; Lister et al, 2008; Lister et al, 2009a; Ziller et al, 2013)
The presence of 5mC oxidation derivatives in mammalian genome makes bisulfite sequencing more complicated, since 5hmC reads as C, same with the 5mC, while both 5fC and 5caC read as T in BS-seq
Summary
Received January 16, 2015; accepted February 27, 2015; published online January 27, 2016. Epigenetic changes caused by DNA methylation and histone modifications play important roles in the regulation of various cellular processes and development. Analysis of DNA modification patterns relies increasingly on sequencing-based profiling methods. A number of different approaches have been established to map the DNA epigenomes with single-base resolution, as represented by the bisulfite-based methods, such as classical bisulfite sequencing (BS-seq), TAB-seq (TET-assisted bisulfite sequencing), oxBS-seq (oxidative bisulfite sequencing) and etc. These methods have been used to generate base-resolution maps of 5mC and its oxidation derivatives in genomic samples. Epigenetics, DNA methylation, bisulfite sequencing (BS-Seq), TAB-seq, oxBS-seq, fC-CET
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