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Hejun Liu

China Novartis Institutes for Biomedical Research, China

Title: Structure-based discovery on the specificities of histone chaperone Hif1

Biography

Hejun Liu has his expertise in structural biology and is focusing on histone chaperones and chromatin structure regulation. He is now an investigator at China Novartis Institutes for Biomedical Research. He has studied SHNi-TPR histone chaperone for years and solved histone chaperone Hif1 structure 3 years ago, which is the first structure of SHNi-TPR family. As he has said that the structure helps a lot in mapping the histone binding pattern of Hif1. Then he reconstituted various Hif1-histone complexes and solved the structure of Hif1 in complex with H2A-H2B. The complex structure revealed a novel chaperone specificity of Hif1 that interacts to both H2A-H2B dimer and H3-H4 tetramer.

Abstract


Eukaryotic genomes are packed hierarchically into chromatins with nucleosomes as their basic repeat units. Histone chaperones involved in this process are critical for guiding specific histone post-translational modifications, safeguarding stepwise nucleosome assembly and disassembly, and thus regulating chromatin structures to change gene activities. Histone chaperone Hif1 (Hat1-interacting factor 1) was first reported to be involved in nuclear histone acetylation complex HAT-B that acetylates histone H4 at lysine K5 and K12 sites. In addition, Hif1 was also reported to be involved in telomere silence and nucleosome (dis)assembly. However, the structural basis of Hif1 and how it interacts to histones remains largely unknown. Hence we take our advantage in protein crystallographic research on Hif1 structure and its complex with core histones to reveal its chaperone specificities on core histones. We first solved the structure of Hif1 and revealed the architecture of SHNi-TPR (Sim3-Hif1-NASP interrupted tetratricopeptide repeat) proteins for the first time. The structure reveals that Hif1 contains a TPR domain formed by 4 TPR helix bundles and an interrupted coil-coiled acid loop that covers the rear surface of the TPR domain. Based on this structure, we demonstrated that both the TPR domain and acid loop are responsible for the histone binding. Hence, we solved the complex structure of Hif1-H2A-H2B-Hif1 to elucidate the chaperone specificity of Hif1. Based on these structure-based discoveries, our data revealed that Hif1 binds both H2A-H2B dimer and H3-H4 tetramer in an alternative binding manner. And this binding pattern is conserved across SHNi-TPR family from yeast to human. Overall, these findings provide clues for investigating the potential roles of SHNi-TPR proteins in nucleosome (dis)assembly.