Mammalian H4K16ac regulates the spatiotemporal order of genome replication rather than gene expression.

ABSTRACT: Histone acetylation is widely assumed to directly instruct gene activation. Among acetylated residues, H4K16ac is one of the most abundant modifications, conserved across all eukaryotes. Despite its established role in X-chromosome hyperactivation in Drosophila, its function in mammalian cells has remained elusive. Here, we show that in human somatic cells, H4K16ac does not substantially affect gene expression, but instead controls the spatiotemporal program of genome replication. By combining a meta-analysis of public datasets and perturbation experiments designed to minimize confounding effects, we found that H4K16ac is neither associated with nor required for transcriptional activity. Rather, H4K16ac depletion resulted in premature replication of heterochromatic regions and widespread a

SUBMITTER: Milan M 

PROVIDER: S-EPMC12455591 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature