3x1v | pdb_00003x1v
Crystal structure of nucleosome core particle in the presence of histone variant involved in reprogramming
Structural highlights
Function[H2B1A_MOUSE] Variant histone specifically required to direct the transformation of dissociating nucleosomes to protamine in male germ cells (PubMed:23884607, PubMed:28366643). Entirely replaces classical histone H2B prior nucleosome to protamine transition and probably acts as a nucleosome dissociating factor that creates a more dynamic chromatin, facilitating the large-scale exchange of histones (PubMed:23884607). In condensing spermatids, the heterodimer between H2AFB1 and HIST1H2BA/TH2B is loaded onto the nucleosomes and promotes loading of transition proteins (TNP1 and TNP2) onto the nucleosomes (PubMed:28366643). Inclusion of the H2AFB1-HIST1H2BA/TH2B dimer into chromatin opens the nucleosomes, releasing the nucleosomal DNA ends and allowing the invasion of nucleosomes by transition proteins (TNP1 and TNP2) (PubMed:28366643). Then, transition proteins drive the recruitment and processing of protamines, which are responsible for histone eviction (PubMed:28366643). Also expressed maternally and is present in the female pronucleus, suggesting a similar role in protamine replacement by nucleosomes at fertilization (PubMed:23884607). Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.[1] [2] Publication Abstract from PubMedHistone variants TH2a and TH2b are highly expressed in testes, oocytes and zygotes. Our recent analysis suggested that these histone variants enhance the induced generation of pluripotent stem cells (iPSCs) when co-expressed along with four transcription factors, Oct3/4, Sox2, Klf4 and c-Myc (OSKM), and are associated with an open chromatin structure [1]. In the present study, we report the crystal structures of nucleosomes (NCPs) with the mouse histone variants, TH2a and TH2b. The structures revealed two significant changes, as compared to the canonical counterparts: fewer histone-DNA contacts and changes in dimer-dimer interactions between TH2a-TH2a' (L1-loop). In vivo studies with domain swapping and point mutants of the variants revealed that the residues in the histone tails and the TH2a-L1 loop are important for reprogramming. Taken together, our work indicates that the NCP variants with structural modifications and flexible tails are most likely important for enhanced reprogramming of functions. Structural and functional analyses of nucleosome complexes with mouse histone variants TH2a and TH2b, involved in reprogramming.,Padavattan S, Shinagawa T, Hasegawa K, Kumasaka T, Ishii S, Kumarevel T Biochem Biophys Res Commun. 2015 Aug 28;464(3):929-35. doi:, 10.1016/j.bbrc.2015.07.070. Epub 2015 Jul 17. PMID:26188507[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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