| Structural highlights
Function
[H2B1J_HUMAN] 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] [3] Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid.[4] [5] [6]
Publication Abstract from PubMed
Centromeric nucleosomes are composed of the centromere-specific histone H3 variant CENP-A and the core histones H2A, H2B, and H4. To establish a functional kinetochore, histone H4 lysine-20 (H4K20) must be monomethylated, but the underlying mechanism has remained enigmatic. To provide structural insights into H4K20 methylation, we here solve the crystal structure of a nucleosome containing an H3.1-CENP-A chimera, H3.1(CATD), which has a CENP-A centromere targeting domain and preserves essential CENP-A functions in vivo. Compared to the canonical H3.1 nucleosome, the H3.1(CATD) nucleosome exhibits conformational changes in the H4 N-terminal tail leading to a relocation of H4K20. In particular, the H4 N-terminal tail interacts with glutamine-76 and aspartate-77 of canonical H3.1 while these interactions are cancelled in the presence of the CENP-A-specific residues valine-76 and lysine-77. Mutations of valine-76 and lysine-77 impair H4K20 monomethylation both in vitro and in vivo. These findings suggest that a CENP-A-mediated structural polymorphism may explain the preferential H4K20 monomethylation in centromeric nucleosomes.
The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism.,Arimura Y, Tachiwana H, Takagi H, Hori T, Kimura H, Fukagawa T, Kurumizaka H Nat Commun. 2019 Feb 4;10(1):576. doi: 10.1038/s41467-019-08314-x. PMID:30718488[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kim HS, Cho JH, Park HW, Yoon H, Kim MS, Kim SC. Endotoxin-neutralizing antimicrobial proteins of the human placenta. J Immunol. 2002 Mar 1;168(5):2356-64. PMID:11859126
- ↑ Tollin M, Bergman P, Svenberg T, Jornvall H, Gudmundsson GH, Agerberth B. Antimicrobial peptides in the first line defence of human colon mucosa. Peptides. 2003 Apr;24(4):523-30. PMID:12860195
- ↑ Howell SJ, Wilk D, Yadav SP, Bevins CL. Antimicrobial polypeptides of the human colonic epithelium. Peptides. 2003 Nov;24(11):1763-70. PMID:15019208 doi:10.1016/j.peptides.2003.07.028
- ↑ Kim HS, Cho JH, Park HW, Yoon H, Kim MS, Kim SC. Endotoxin-neutralizing antimicrobial proteins of the human placenta. J Immunol. 2002 Mar 1;168(5):2356-64. PMID:11859126
- ↑ Tollin M, Bergman P, Svenberg T, Jornvall H, Gudmundsson GH, Agerberth B. Antimicrobial peptides in the first line defence of human colon mucosa. Peptides. 2003 Apr;24(4):523-30. PMID:12860195
- ↑ Howell SJ, Wilk D, Yadav SP, Bevins CL. Antimicrobial polypeptides of the human colonic epithelium. Peptides. 2003 Nov;24(11):1763-70. PMID:15019208 doi:10.1016/j.peptides.2003.07.028
- ↑ Arimura Y, Tachiwana H, Takagi H, Hori T, Kimura H, Fukagawa T, Kurumizaka H. The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism. Nat Commun. 2019 Feb 4;10(1):576. doi: 10.1038/s41467-019-08314-x. PMID:30718488 doi:http://dx.doi.org/10.1038/s41467-019-08314-x
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