Structure of human nucleosome containing the testis-specific histone variant TSH2B

Abstract

PDB reference: TSH2B nucleosome, 3wkjThe human histone H2B variant TSH2B is highly expressed in testis and may function in the chromatin transition during spermatogenesis. In the present study, the crystal structure of the human testis-specific nucleosome containing TSH2B was determined at 2.8 Å resolution. A local structural difference between TSH2B and canonical H2B in nucleosomes was detected around the TSH2B-specific amino-acid residue Ser85. The TSH2B Ser85 residue does not interact with H4 in the nucleosome, but in the canonical nucleosome the H2B Asn84 residue (corresponding to the TSH2B Ser85 residue) forms watermediated hydrogen bonds with the H4 Arg78 residue. In contrast, the other TSH2B-specific amino-acid residues did not induce any significant local structural changes in the TSH2B nucleosome. These findings may provide important information for understanding how testis-specific histone variants form nucleosomes during spermatogenesis.

Differential localization of histone variant TH2B during the first round compared with subsequent rounds of spermatogenesis

“…These differences likely arise from variation in fixation protocols, immunostaining procedures as well as mouse strains used. However, it is worth noting that a majority of the analyses demonstrating that TH2B is localized initially to spermatocytes was discovered using the adult rat . These data are consistent with our findings that after the first spermatocytes appear, TH2B switches its localization from the spermatogonia to the spermatocyte population.…”

“…The incorporation of these histone variants enables the tight regulation of gene expression programs that are critical to spermatogenetic processes such as DNA repair and meiotic recombination . These histone variants are replaced by transition proteins, which are then replaced with protamines . The tight wrapping of the chromatin around protamines results in a highly condensed structure that fits into the small sperm nucleus.…”

“…1,2,4 These histone variants are replaced by transition proteins, which are then replaced with protamines. [5][6][7] The tight wrapping of the chromatin around protamines results in a highly condensed structure that fits into the small sperm nucleus. Of the many testis-specific histone variants that have been identified, the testis-specific histone H2B variant (TH2B) and the testis-specific histone H2A variant (TH2A) are of particular interest, because the incorporation of these variants into the nucleosome core particle results in a globally open, more accessible chromatin structure.…”

Structural and functional analyses of nucleosome complexes with mouse histone variants TH2a and TH2b, involved in reprogramming

“…Intriguingly, closer inspections of the variant NCPs (GCH, GCHV1, and GCHV2) revealed two changes: fewer histone-DNA contacts and significant changes in the L1-L1 0 loop interactions between the TH2a-TH2a 0 dimers. Recently, chromatin structure containing the human histone H2B variant TSH2B was reported and the overall structural composition is similar to our GCHV1 [26].…”

“…In the cross variant GCHV1-NCP, the H2b-His83 side-chain adopts a conformation similar to that in GCH, and thus has lost the contact with the interface. Also, it is noteworthy to mention that we did not observe any structural changes around the residue Asn84 (Ser85 in TSH2B) of TH2B in GCH or GHV2 nucleosome structures, when compared to TSH2B [26]. In GCHV2-NCP, the L1-L1 0 interface has three H-bonds and resembles the canonical-NCP.…”