Acidic nucleoplasmic DNA-binding protein (And-1) controls chromosome congression by regulating the assembly of centromere protein A (CENP-A) at centromeres

Abstract

Background: The incorporation of CENP-A at centromeres is important for chromosome segregation during mitosis. Results: And-1 together with HJURP regulates the assembly of new CENP-A onto centromeres. Conclusion: And-1 facilitates the recruitment of CENP-A to centromeres. Significance: These studies reveal a novel role of And-1 in the regulation of chromosome congression during mitosis. The centromere is an epigenetically designated chromatin domain that is essential for the accurate segregation of chromosomes during mitosis. The incorporation of centromere protein A (CENP-A) into chromatin is fundamental in defining the centromeric loci. Newly synthesized CENP-A is loaded at centromeres in early G1 phase by the CENP-A-specific histone chaperone Holliday junction recognition protein (HJURP) coupled with other chromatin assembly factors. However, it is unknown whether there are additional HJURP-interacting factor(s) involving in this process. Here we identify acidic nucleoplasmic DNA-binding protein 1 (And-1) as a new factor that is required for the assembly of CENP-A nucleosomes. And-1 interacts with both CENP-A and HJURP in a prenucleosomal complex, and the association of And-1 with CENP-A is increased during the cell cycle transition from mitosis to G1 phase. And-1 down-regulation significantly compromises chromosome congression and the deposition of HJURP-CENP-A complexes at centromeres. Consistently, overexpression of And-1 enhances the assembly of CENP-A at centromeres. We conclude that And-1 is an important factor that functions together with HJURP to facilitate the cell cycle-specific recruitment of CENP-A to centromeres. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.