The role of the histone chaperone ASF1 in recycling parental histones during DNA replication

In eukaryotes, DNA wraps around proteins called histones to form chromatin. This structure allows, first, the compaction of the genome in the nucleus, but also the regulation of its expression. Indeed, histones can be a source of information referred to as “epigenetic”: they exist under different forms, histone variants, and can have post-translational modifications. The presence of these variants and modifications organizes the genome into domains with different transcriptional status.DNA replication destabilizes chromatin structure and, therefore, represents a challenge for the cell, which must duplicate its genetic material while also transmitting its epigenetic landscape in order to maintain its identity. In this context, recycling parental histones is essential to faithfully transmit histone variants and their modifications.During my PhD, I tried to address the question: how are the histone variants H3.1 and H3.3 recycled during DNA replication? In particular, I investigated the role of the histone chaperone Anti-Silencing Function 1 (ASF1) in this process.My approach was to develop a super-resolution microscopy technique (STORM) to visualize parental histone variants precisely at replication sites. Using this technology, I could study the impact of ASF1 depletion on the recycling of parental histones, and further our understanding of fundamental mechanisms that transmit epigenetic information.