Non-nucleosomal (CENP-A/H4)2 - DNA complexes as a possible platform for centromere organization

The centromere is a part of the chromosome that is essential for the even segregation of duplicated chromosomes during cell division. It is epigenetically defined by the presence of the histone H3 variant CENP-A. CENP-A associates specifically with a group of 16 proteins that form the centromere-associated network of proteins (CCAN). In mitosis, the kinetochore forms on the CCAN to connect the duplicated chromosomes to the microtubules protruding from the cell poles. Previous studies have shown that CENP-A replaces H3 in nucleosomes, and recently the structures of CENP-A-containing nucleosomes in complex with CCANs have been revealed, but they show only a limited interaction between CCANs and CENP-A. Here, we report the cryoEM structure of 2x(CENP-A/H4)2-di-tetramers assembled on DNA in the absence of H2A/H2B histone dimer and speculate how (CENP-A/H4)2-tetramers and -di-tetramers might serve as a platform for CCAN organization. Main pointsO_LICENP-A/H4 in the absence of H2A/H2B dimers associate on DNA to form di-tetrasomes C_LIO_LICENP-A/H4 di-tetrasomes are stable but highly flexible structures resembling nucleosomes C_LIO_LICENP-A/H4 tetrasomes bind CENP-N/L and can serve as platform for centromere organisation C_LI