MOE Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: [Email]
Histone readers recognize histone modifications and mediate downstream biological events. A series of strategies to identify new histone readers have been developed and improved recently. Asides from the traditional pull-down methods and protein structure/function based educated guess, crosslinking and high-throughput screening based strategies led to the discovery of many new histone readers. In this review, we reviewed the rationale and applications of photo-affinity lysine based crosslinking strategies and array/designer nucleosome libraries based high-throughput screening strategies. Epigenome editing technologies to incorporate histone modifications in cells were also discussed. Finally, we summarized the newly identified histone readers (e.g. ZZ domain and Agenet domain) and histone modifications (e.g. serotonylation and benzoylation).