9k9l
From Proteopedia
Cryo-EM structure of the human CENP-A-H4 octasome.
Structural highlights
FunctionCENPA_HUMAN Histone H3-like variant which exclusively replaces conventional H3 in the nucleosome core of centromeric chromatin at the inner plate of the kinetochore. Required for recruitment and assembly of kinetochore proteins, mitotic progression and chromosome segregation. May serve as an epigenetic mark that propagates centromere identity through replication and cell division. The CENPA-H4 heterotetramer can bind DNA by itself (in vitro).[1] [2] Publication Abstract from PubMedIn eukaryotes, genomic DNA is stored in the nucleus as nucleosomes, in which a DNA segment is wrapped around a protein octamer consisting of two each of the four histones, H2A, H2B, H3, and H4. The core histones can be replaced by histone variants or altered with covalent modifications, contributing to the regulation of chromosome structure and nuclear activities. The formation of an octameric histone core in nucleosomes is widely accepted. Recently, the H3-H4 octasome, a novel nucleosome-like structure with a histone octamer consisting solely of H3 and H4, has been reported. CENP-A is the centromere-specific histone H3 variant and determines the position of kinetochore assembly during mitosis. CENP-A is a distant H3 variant sharing approximately 50% amino acid sequence with H3. In this study, we found that CENP-A and H4 also formed an octamer without H2A and H2B in vitro. We determined the structure of the CENP-A-H4 octasome at 3.66 A resolution. In the CENP-A-H4 octasome, an approximately 120-base pair DNA segment was wrapped around the CENP-A-H4 octameric core and displayed the four CENP-A RG-loops, which are the direct binding sites for another centromeric protein, CENP-N. Cryo-EM Analysis of a Unique Subnucleosome Containing Centromere-Specific Histone Variant CENP-A.,Kawasaki O, Takizawa Y, Kiyokawa I, Kurumizaka H, Nozawa K Genes Cells. 2025 Mar;30(2):e70016. doi: 10.1111/gtc.70016. PMID:40129080[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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