Noncoding transcription influences replication timing/efficiency by modulating ARS chromatin structure and ORC binding. The chromatin structure of replication origins is defined, at least in part, by the level of pervasive readthrough transcription. In the presence of efficient noncoding (Nrd1/Nab3/Sen1-dependent) or mRNA (CPF/CF-dependent) transcription termination, ARSs present low H3K36 trimethylation, high downstream nucleosome acetylation (Ac), a wide NDR, and more ORC binding at the ACS, favoring early and efficient replication. If transcription termination is deficient, H3K36me3 by Set2 increases and histone acetylation decreases, likely through the recruitment of the Rpd3 histone deacetylase; these modifications increase nucleosome stability and occupancy over the ARS, lowering the level of ORC recruitment and resulting in late and inefficient ARS replication.
