Kurumizaka lab revealed the atomic structure of the human testis-specific nucleosome

WASEDA UNIVERSITY Faclty of Science and Engineering
Graduate School of Advanced Science and Engineering
Department of Electrical Engineering and Biocience
Prof.Hitoshi Kurumizaka

“Faculty of Science and Engineering, Kurumizaka lab, has reported that
the first atomic structure of the human testis-specific nucleosome. ”

In eukaryotes, the chromatin structure functions in the compaction of the huge amount of genomic DNA within the nucleus, and the nucleosome is the fundamental repeating unit of chromatin. Nucleosome is composed of a histone octamer and a 146 base-pair DNA, which is wrapped around the histone octamer. The histone octamer contains two each of the core histones, H2A, H2B, H3, and H4. A histone H3 variant, H3T, is a mysterious histone variant, which is highly expressed in the testis. However, almost no information about the biochemical and structural properties of H3T has been reported so far, even though H3T is considered to play an important role in the chromatin reorganization required for meiosis and/or spermatogenesis. A recent finding showed that, in humans, about 4% of the haploid genome in the sperm is retained in the nucleosomes, with some containing testis-specific histone variants. This observation suggests that testis-specific histone variants may function as epigenetic markers in the sperm chromatin. Therefore, H3T is one of the most topical and important histone variants to understand not only meiosis and spermatogenesis, but also epigenetic inheritance through the sperm chromatin.
Here we discovered that the nucleosome containing human H3T is significantly unstable, as compared to the conventional nucleosome containing H3, both in vitro and in vivo. The crystal structure of the H3T nucleosome revealed that the H3T regions, which exhibited structural differences from those of the conventional H3 structure, were important for the instability of the H3T nucleosomes. Mutational analyses indicated that the H3T-specific residues (Met71 and Val111), which are the source of the structural differences between H3T and H3.1, are responsible for the reduced stability of the H3T nucleosome. These physical and structural properties of the H3T-containing nucleosome may provide the basis of chromatin reorganization during spermatogenesis.

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