Single-cell epigenomics: powerful new methods for understanding gene regulation and cell identity.

Stephen J Clark,Wolf Reik,Sébastien A Smallwood,Gavin Kelsey,Heather J Lee

doi:10.1186/s13059-016-0944-x

Abstract

Emerging single-cell epigenomic methods are being developed with the exciting potential to transform our knowledge of gene regulation. Here we review available techniques and future possibilities, arguing that the full potential of single-cell epigenetic studies will be realized through parallel profiling of genomic, transcriptional, and epigenetic information.

Highlights

Epigenetics involves the study of regulatory systems that enable heritable changes in gene expression within genotypically identical cells
While investigation of DNA methylation at the singlecell level was motivated by important biological questions, until recently it was unfeasible due to the large amount of DNA degradation caused by the bisulfite conversion, which was traditionally performed after preparing adapter-tagged libraries
Chromatin structure and chromosome organization A raft of publications was seen in 2015 describing methods for mapping open chromatin in single cells

Summary

Introduction

Epigenetics involves the study of regulatory systems that enable heritable changes in gene expression within genotypically identical cells This includes chemical modifications to DNA and the associated histone proteins, as well as changes in DNA accessibility and chromatin conformation [1]. Cytosine methylation and other DNA modifications DNA methylation of cytosine (5mC) residues can be mapped genome-wide using several methods such as methylation-specific restriction enzymes [3], affinity purification [4], or by using bisulfite conversion followed by sequencing (BS-seq) [5] The latter is considered the gold-standard method as it allows single base resolution and absolute quantification of DNA methylation levels. While investigation of DNA methylation at the singlecell level was motivated by important biological questions, until recently it was unfeasible due to the large amount of DNA degradation caused by the bisulfite conversion, which was traditionally performed after preparing adapter-tagged libraries

Method

Findings

Conclusions