Histone modifications during acute S-phase defects

ABSTRACT: Long-term perturbation of de novo chromatin assembly during DNA replication has profound effects on epigenome maintenance and cell fate. The early mechanistic origin of these functional defects is unknown. Here, we combine acute degradation of Chromatin Assembly Factor 1 (CAF-1), a key player in de novo chromatin assembly during DNA replication and analyse effects n histone modifications by mass spectrometry. Immediately upon CAF-1 depletion from human TERT-RPE-1 cells, we observe an acute cellular response affecting histone repertoire, global chromatin composition and transcriptional fidelity resulting in a p53-dependent cell cycle arrest. Our work reveals the immediate local and global consequences of defective de novo chromatin assembly during DNA replication, explaining how at later times the epigenome and cell fate can be altered.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

SUBMITTER: Moritz Voelker-Albert  

LAB HEAD: Francesca Mattiroli

PROVIDER: PXD050618 | Pride | 2024-11-14

REPOSITORIES: Pride