Dynamic chromosomal interactions and control of heterochromatin positioning by Ki-67.
EMBO Rep
; 23(12): e55782, 2022 12 06.
Article
em En
| MEDLINE
| ID: mdl-36245428
ABSTRACT
Ki-67 is a chromatin-associated protein with a dynamic distribution pattern throughout the cell cycle and is thought to be involved in chromatin organization. The lack of genomic interaction maps has hampered a detailed understanding of its roles, particularly during interphase. By pA-DamID mapping in human cell lines, we find that Ki-67 associates with large genomic domains that overlap mostly with late-replicating regions. Early in interphase, when Ki-67 is present in pre-nucleolar bodies, it interacts with these domains on all chromosomes. However, later in interphase, when Ki-67 is confined to nucleoli, it shows a striking shift toward small chromosomes. Nucleolar perturbations indicate that these cell cycle dynamics correspond to nucleolar maturation during interphase, and suggest that nucleolar sequestration of Ki-67 limits its interactions with larger chromosomes. Furthermore, we demonstrate that Ki-67 does not detectably control chromatin-chromatin interactions during interphase, but it competes with the nuclear lamina for interaction with late-replicating DNA, and it controls replication timing of (peri)centromeric regions. Together, these results reveal a highly dynamic choreography of genome interactions and roles for Ki-67 in heterochromatin organization.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Heterocromatina
/
Genômica
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article