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- Title
CAF-1 and Rtt101p function within the replication-coupled chromatin assembly network to promote H4 K16ac, preventing ectopic silencing.
- Authors
Young, Tiffany J.; Cui, Yi; Pfeffer, Claire; Hobbs, Emilie; Liu, Wenjie; Irudayaraj, Joseph; Kirchmaier, Ann L.
- Abstract
Replication-coupled chromatin assembly is achieved by a network of alternate pathways containing different chromatin assembly factors and histone-modifying enzymes that coordinate deposition of nucleosomes at the replication fork. Here we describe the organization of a CAF-1-dependent pathway in Saccharomyces cerevisiae that regulates acetylation of histone H4 K16. We demonstrate factors that function in this CAF-1-dependent pathway are important for preventing establishment of silenced states at inappropriate genomic sites using a crippled HMR locus as a model, while factors specific to other assembly pathways do not. This CAF-1-dependent pathway required the cullin Rtt101p, but was functionally distinct from an alternate pathway involving Rtt101p-dependent ubiquitination of histone H3 and the chromatin assembly factor Rtt106p. A major implication from this work is that cells have the inherent ability to create different chromatin modification patterns during DNA replication via differential processing and deposition of histones by distinct chromatin assembly pathways within the network. Author summary: Replication-coupled chromatin assembly occurs via a network of alternate pathways through which histones are processed, and chromatin is disassembled in front of the replication fork, then reassembled behind the fork to ensure the inheritance of appropriate epigenetic states. Yet, despite being essential for maintaining cell identity across cell generations, the organization of this network and what distinct functions individual pathways within this network may play has remained poorly understood. Here, we have used molecular genetic and live cell protein-protein interaction strategies to probe this network. We highlight a CAF-1-dependent pathway with a unique role in regulating histone H4 K16ac to prevent the establishment of epigenetically silenced states at ectopic sites. We also discovered the cullin Rtt101p functions in this CAF-1-dependent pathway in a manner distinct from Rtt101p's role in promoting chromatin assembly along a Rtt106p-dependent pathway via ubiquitination of histone H3. Our findings illustrate that cells use alternate chromatin assembly pathways within the network during DNA replication to create distinct chromatin modification patterns. These patterns, in turn, influence the probability of establishing new epigenetic states.
- Subjects
HISTONES; CHROMATIN; DNA replication; HISTONE acetylation; PREVENTION
- Publication
PLoS Genetics, 2020, Vol 16, Issue 12, p1
- ISSN
1553-7390
- Publication type
Article
- DOI
10.1371/journal.pgen.1009226