In the past decades, histones, once considered by many as “The World‘s Most Boring Protein” has rejuvenated, thanking for the discovery of various covalent modifications. A “histone code” was hypothesized that specific pattern of modifications on histones can be read and written as a code by protein executors to carry out specific biological function. In addition to the individual and combinatorial effects of different modifications, another layer of complexity is created by how these histone markers are regulated temporally and spatially, which has not been fully explored. Furthermore, the journey to understand the function of histone modifications including their modifying enzymes in certain biological processes such as meiosis, development, tumorigenesis and aging just gets started. On the other hand, another unsolved question in the filed is how many markers occur on a given histone or nucleosome simultaneously and how could they affect higher-order chromatin structure/organization.

In the past few years, we have established versatile histone H3/H4 and H2A/H2B mutant library in yeast to study histone related DNA-damage response, genome stability and synthetic lethal interactions, etc. Besides, we focus on newly identified histone modifications, such as H4K8hib both on biological mechanism investigation and regulatory network mapping. Proliferating cell nuclear antigen (PCNA), encoded by POL30 in Saccharomyces cerevisiae, is one of the key components in DNA metabolism. We synthesized a library of PCNA mutant to probe PCNA functions during DNA replication. In all, we are interested in combining genetics, biochemistry and other tools to study the regulatory mechanism of epigenetics.