Profiling chromatin regulatory landscape: insights into the development of ChIP-seq and ATAC-seq
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REVIEW
Molecular Biomedicine
Open Access
Profiling chromatin regulatory landscape: insights into the development of ChIP-seq and ATAC-seq Shaoqian Ma and Yongyou Zhang*
Abstract Chromatin regulatory landscape plays a critical role in many disease processes and embryo development. Epigenome sequencing technologies such as chromatin immunoprecipitation sequencing (ChIP-seq) and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) have enabled us to dissect the pangenomic regulatory landscape of cells and tissues in both time and space dimensions by detecting specific chromatin state and its corresponding transcription factors. Pioneered by the advancement of chromatin immunoprecipitation-chip (ChIP-chip) technology, abundant epigenome profiling technologies have become available such as ChIP-seq, DNase I hypersensitive site sequencing (DNase-seq), ATAC-seq and so on. The advent of single-cell sequencing has revolutionized the next-generation sequencing, applications in single-cell epigenetics are enriched rapidly. Epigenome sequencing technologies have evolved from low-throughput to high-throughput and from bulk sample to the single-cell scope, which unprecedentedly benefits scientists to interpret life from different angles. In this review, after briefly introducing the background knowledge of epigenome biology, we discuss the development of epigenome sequencing technologies, especially ChIP-seq & ATAC-seq and their current applications in scientific research. Finally, we provide insights into future applications and challenges. Keywords: Chromatin regulatory landscape, Epigenome sequencing, Single cell, Developmental biology
Introduction The genome is packaged by histone proteins that are decorated with a wide variety of modifications. Histone acetylation is one of the best-characterized chromatin modifications and correlates with the opening of local chromatin structures and transcriptional activation (e.g., H3K27ac correlates with enhancers) [1]. Compared with histone acetylation, histone methylation is more diverse in terms of both functions and forms. Histon methylation includes H3K4me1, H3K4me3, H3K9me3, H3K36, H3K79, etc. Specific methylation of lysines can exist as monomethylation, dimethylation or trimethylation with different functions [2]. Repressive histone methylation, such as H3K9me3, is highly associated with condensed and constitutive heterochromatin [3]. Meanwhile, active histone methylation such as * Correspondence: [email protected] School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, China
H3K4me3 contributes to active transcription. Several studies even revealed a class of bivalent chromatin with both active and repressive features, which exhibits overlapping patterns of H3K4me3 and H3K27me3 [4]. The discovery of the bivalent signature of such poised genes was unexpected and very important. For instance, it can be a critical landmark in the maternal-to-zygotic transition process, providing the first clues about the “intermediate” state [
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