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Transcription alters Chromatin to Negatively Influence Replication Initiation
Author(s) -
Carlile Candice Marie,
Cook Jean Gowen
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.885.1
Subject(s) - pre replication complex , origin recognition complex , biology , chromatin , licensing factor , control of chromosome duplication , dna replication factor cdt1 , eukaryotic dna replication , dna replication , replication timing , histone , genetics , microbiology and biotechnology , origin of replication , dna re replication , minichromosome maintenance , transcription (linguistics) , dna , linguistics , philosophy
DNA replication begins at many defined sites in the genome called origins of replication. These origins must be spaced throughout the genome to complete DNA replication in a timely manner, but it's clear that origin activity is excluded from certain regions of the genome, such as gene bodies. Here, we show that chromatin modifications contribute to preventing replication initiation within gene bodies. We recapitulated previous findings that transcription through an origin inhibits replication initiation from that origin. We examined if transcription machinery inhibits replication by: (1) physically displacing replication factors or (2) constructing a chromatin environment incompatible for replication initiation. Interestingly, we eliminate this inhibition of origin activity by deleting Set2, a histone methyltransferase that co‐transcriptionally adds methyl groups to histone H3 K36. These data suggest that methylation at H3K36 impedes replication initiation. In addition, artificially tethering Set2, but not catalytically dead Set2 near a plasmid‐born origin of replication, inhibits the ability of that origin to initiate DNA replication. These results suggest that transcription‐induced chromatin changes prevent replication initiation from an origin of replication. Mechanistic studies will elucidate how this methylation impacts the recruitment of replication proteins to prevent initiation.