The histone deacetylase inhibitor trichostatin A alters the pattern of DNA replication origin activity in human cells.

ABSTRACT: Eukaryotic chromatin structure limits the initiation of DNA replication spatially to chromosomal origin zones and temporally to the ordered firing of origins during S phase. Here, we show that the level of histone H4 acetylation correlates with the frequency of replication initiation as measured by the abundance of short nascent DNA strands within the human c-myc and lamin B2 origins, but less well with the frequency of initiation across the beta-globin locus. Treatment of HeLa cells with trichostatin A (TSA) reversibly increased the acetylation level of histone H4 globally and at these initiation sites. At all three origins, TSA treatment transiently promoted a more dispersive pattern of initiations, decreasing the abundance of nascent DNA at previously preferred initiation sites while in

SUBMITTER: Kemp MG 

PROVIDER: S-EPMC546162 | biostudies-literature | 2005

REPOSITORIES: biostudies-literature