EpiMethylTag: simultaneous detection of ATAC-seq or ChIP-seq signals with DNA methylation

Priscillia Lhoumaud,Matthias Stadtfeld,Valentina Snetkova,Kyu-Tae Kim,Effie Apostolou,Dafne Campigli Di Giammartino,Simon Vidal,Theodore Sakellaropoulos,Jane Skok,Macintosh Cornwell,Gunjan Sethia,Franco Izzo,Dan Avi Landau,Sana Badri

doi:10.1186/s13059-019-1853-6

Priscillia Lhoumaud, Matthias Stadtfeld + Show 12 more

Open Access

https://doi.org/10.1186/s13059-019-1853-6

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Abstract

Activation of regulatory elements is thought to be inversely correlated with DNA methylation levels. However, it is difficult to determine whether DNA methylation is compatible with chromatin accessibility or transcription factor (TF) binding if assays are performed separately. We developed a fast, low-input, low sequencing depth method, EpiMethylTag, that combines ATAC-seq or ChIP-seq (M-ATAC or M-ChIP) with bisulfite conversion, to simultaneously examine accessibility/TF binding and methylation on the same DNA. Here we demonstrate that EpiMethylTag can be used to study the functional interplay between chromatin accessibility and TF binding (CTCF and KLF4) at methylated sites.

Highlights

The role of DNA methylation (DNAme) in gene regulation has been widely described [1,2,3,4]
To circumvent the high input and sequencing expenses associated with Whole-genome bisulfite sequencing (WGBS) and existing ChIP combined with bisulfite conversion protocols [10,11,12], we developed “EpiMethylTag.” This technique combines ATAC-seq or ChIPmentation [13, 14] with bisulfite conversion (M-ATAC or M-ChIP, respectively) to determine the methylation status of accessible or transcription factor (TF)-bound regions in a chromatin context
EpiMethylTag is a reproducible method for testing the compatibility of DNAme with TF binding or chromatin accessibility M-ATAC and CTCF M-ChIP were performed in duplicate on murine embryonic stem cells

Summary

Introduction

The role of DNA methylation (DNAme) in gene regulation has been widely described [1,2,3,4]. We still know very little about the DNA sequence and chromatin context of TF binding at methylated sites and its significance to gene regulation. The alternative, reduced representation bisulfite sequencing (RRBS), To circumvent the high input and sequencing expenses associated with WGBS and existing ChIP combined with bisulfite conversion protocols [10,11,12], we developed “EpiMethylTag.” This technique combines ATAC-seq or ChIPmentation [13, 14] with bisulfite conversion (M-ATAC or M-ChIP, respectively) to determine the methylation status of accessible or TF-bound regions in a chromatin context. EpiMethylTag is based on an approach that was originally developed for tagmentation-based

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Conclusion