Protein-only centromeric chromatin assembly streamlines human artificial chromosome formation.

ABSTRACT: Human artificial chromosomes (HACs) are inherited through cell divisions alongside natural chromosomes, serving as tools for interrogating chromosomal elements and as vectors for large genetic cargoes (1-5). Despite recent progress (6-8), large (i.e., multiple Mb) HACs have not been reported. Further, HAC formation via epigenetic seeding of centromeric chromatin currently requires prior engineering of recipient human cells (6-8), hampering their potential deployment in many useful cell types. Here, we designed, built, and delivered to human cells a 2 Mb HAC construct that is ~3 times larger than the prior generation. We also report a robust epigenetic centromere seeding approach that initiates immediately upon delivery to the human cell cytoplasm and bypasses genetic engineering of target

SUBMITTER: Birchak GJ 

PROVIDER: S-EPMC12873790 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature