by Marta Radman-Livaja, Kitty F. Verzijlbergen, Assaf Weiner, Tibor van Welsem, Nir Friedman, Oliver J. Rando, Fred van Leeuwen
Replicating chromatin involves disruption of histone-DNA contacts and subsequent
reassembly of maternal histones on the new daughter genomes. In bulk, maternal
histones are randomly segregated to the two daughters, but little is known about
the fine details of this process: do maternal histones re-assemble at preferred
locations or close to their original loci? Here, we use a recently developed
method for swapping epitope tags to measure the disposition of ancestral histone
H3 across the yeast genome over six generations. We find that ancestral H3 is
preferentially retained at the 5′ ends of most genes, with strongest
retention at long, poorly transcribed genes. We recapitulate these observations
with a quantitative model in which the majority of maternal histones are
reincorporated within 400 bp of their pre-replication locus during replication,
with replication-independent replacement and transcription-related retrograde
nucleosome movement shaping the resulting distributions of ancestral histones.
We find a key role for Topoisomerase I in retrograde histone movement during
transcription, and we find that loss of Chromatin Assembly Factor-1 affects
replication-independent turnover. Together, these results show that specific
loci are enriched for histone proteins first synthesized several generations
beforehand, and that maternal histones re-associate close to their original
locations on daughter genomes after replication. Our findings further suggest
that accumulation of ancestral histones could play a role in shaping histone
modification patterns.
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