Open AccessMultiplexed and Ultralow-Input ChIP-seq Enabled by Tagmentation-Based Indexing and Facile Microfluidics
Author(s) -
Chengyu Deng,
Travis Murphy,
Qiang Zhang,
Lynette B. Naler,
Alice Xu,
Chao Lu
Publication year - 2020
Publication title -
analytical chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.117
H-Index - 332
eISSN - 1520-6882
pISSN - 0003-2700
DOI - 10.1021/acs.analchem.0c02550
Subject(s) - epigenome , microfluidics , histone , chromatin immunoprecipitation , computational biology , profiling (computer programming) , epigenomics , epigenetics , chemistry , chip , dna sequencing , multiplexing , chromatin , gene expression profiling , dna methylation , dna , nanotechnology , computer science , gene , gene expression , biology , materials science , biochemistry , telecommunications , promoter , operating system
Epigenome constitutes an important layer that regulates gene expression and dynamics during development and diseases. Extensive efforts have been made to develop epigenome profiling methods using a low number of cells and with high throughput. Chromatin immunoprecipitation (ChIP) is the most important approach for profiling genome-wide epigenetic changes such as histone modifications. In this report, we demonstrate microfluidic ChIPmentation (mu-CM), a microfluidic technology that enables profiling cell samples that individually do not generate enough ChIP DNA for sequencing library preparation. We used a simple microfluidic device to allow eight samples to be processed simultaneously. The samples were indexed differently using a tagmentation-based approach (ChIPmentation) and then merged for library preparation. A histone modification profile for each individual sample was obtained by demultiplexing the sequencing reads based on the indexes. Our technology allowed profiling 20 cells and is well suited for cell-type-specific studies using low-abundance tissues.