Abstract:

The chromosome immunoprecipitation sequencing technology（ChIP-seq）, which combines the chromatin immunoprecipitation technology（ChIP）with the second generation sequencing technology，is an important method for analyzing the epigenetic changes of the whole genome，and can quickly and effectively detect DNA and protein binding sites，transcription factor binding sites（TFBS），histone post-translation modifications（hPTMs），nucleosome localization and DNA methylation in the whole genome. However，for a long time，ChIP-seq needs a large number of cells to generate high-quality data sets，which limits the application of ChIP in some specific tissue and low-cell samples such as oocytes，early embryonic cells and other research fields. In recent years, based on ChIP，researchers have proposed a series of low-input ChIP-seq methods to reduce the initial sample amount and experimental cost and increase the sequencing quality，which has promoted the development of epigenomics. In this paper, we reviewed the principles of ChIP and the methodological development of ChIP-seq reducing low-input amount，compared several of the more important methods，and summarized the application of ChIP-seq with low-input amount in epigenetic research. Finally，we prospected the application and development of low initial ChIP-seq technology，aiming to provide reference for the selection of different low-input ChIP-seq methods for low cell number samples.

Key words: low-input, chromatin co-immunoprecipitation, ChIP-seq, transcription factors, histone modifications