GSE262518 Acute multi-level response to defective de novo chromatin assembly in S-phase

Contributors : Giulia Ricci ; Vivek Bhardwaj ; Jeroen van den Berg ; Francesca MattiroliSeries Type : Genome binding/occupancy profiling by high throughput sequencing ; OtherOrganism : Homo sapiensLong-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 defects is unknown. Here, we combine acute degradation of Chromatin Assembly Factor 1 (CAF-1), a key player in de novo chromatin assembly, with single-cell genomics, quantitative proteomics, and live-microscopy to uncover these initiating mechanisms in human cells. CAF-1 loss immediately slows down DNA replication speed and renders nascent DNA hyper-accessible. A rapid cellular response, distinct from canonical DNA damage signaling, is triggered and lowers histone mRNAs. As a result, histone variants usage and their modifications are altered, limiting transcriptional fidelity and delaying chromatin maturation within a single S-phase. This multi-level response induces a cell-cycle arrest after mitosis. Our work reveals the immediate consequences of defective de novo chromatin assembly during DNA replication, explaining how at later times the epigenome and cell fate can be altered.

Source: GEO: Gene Expression Omnibus - April 17, 2024 Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Other Homo sapiens Source Type: research