Innovative solutions to study epigenetic modifications in disease

Epigenetics is the study of functional modifications to the genome that do not change the DNA sequence. Epigenetic modifications are a major determining factor in cellular differentiation, growth, disease progression and therapeutic response. Along with environmental factors, such as diet and stress, changes in the epigenome regulate gene expression and genome organization and may have profound impacts on cancer and other complex diseases. However, very little is known about which genes are turned on or off, the role of epigenetics in heritability, or how these changes can lead to disease onset. Whether working with single cells or picogram-level inputs from small amounts of complex tissue, Swift offers sensitivity and robust technologies help you unlock challenging samples to make bigger, faster scientific breakthroughs.

DNA methylation is the most widely studied epigenetic modification. DNA methylation occurs mainly on cytosine bases in the CpG dinucleotide motif in mammalian genomes, and across all cytosine contexts in plant genomes. DNA methylation is often associated with the regulation of gene expression through its presence or absence in CpG Islands among gene promoter regions, and these methylation patterns can be used to identify different cell types.  Swift offers the next-generation sequencing (NGS) library preparation solution Accel-NGS Methyl-Seq for methylation sequencing methods of whole genome bisulfite sequencing (WGBS), reduced representation bisulfite sequencing (RRBS) and targeted bisulfite sequencing through hybridization capture methods. The kit’s post-bisulfite library preparation workflow offers the most efficient library preparation method to enable low input quantities such as liquid biopsy from cell free DNA for oncology studies (references). Additionally, the Accel-NGS Adaptase Module enables researchers to prepare single-cell methyl-seq libraries that is currently being utilized to discover neuronal diversity in the mammalian brain (reference SnmC-Seq 1 and 2).

Histone post-translational modifications are another commonly studied epigenetic modification that are important in genome regulation and function. Modifications to histone N-terminal tails, such as methylation and acetylation, regulate how DNA is organized and packaged through the recruitment of additional histone modifying proteins. The presence of specific modifications is indicative of open or closed chromatin confirmations and can be used to study transcriptional regulation. These epigenetic modifications are often assayed by chromatin immunoprecipitation sequencing (ChIP-Seq) which uses antibody pull-down of crosslinked DNA-histone protein followed by deep sequencing. Swift offers NGS library preparation solutions for ChIP-Seq and chromosome confirmation assays, like HiC , through the use of Accel-NGS 2S Plus DNA Library kits. The kit’s unique 5’ and 3’ end repair combined with high efficiency adapter ligation at ultra low input enable low cell number ChIP and HiC studies from picogram DNA input quantities that is not feasible with other DNA library prep kits.


Image credit: Rand Jirtle and Dana Dolinoy

Figure Legend: Epigenetic regulation of the agouti gene in mice, where DNA methylation allows for proper gene expression, while loss of methylation results in genetically identical mice with different coat color, obesity and disease predisposition.


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