ATAD2 is a generalist facilitator of chromatin dynamics in embryonic stem cells

Although the conserved AAA ATPase and bromodomain factor, ATAD2, has been described as a transcriptional co-activator upregulated in manycancers, its functionremains poorly understood.Here, using a combination of ChIP-seq, ChIP-proteomics, and RNA-seqexperiments inembryonic stem cells where Atad2 is normally highly expressed, we found that Atad2 is an a bundant nucleo some-bound protein present onactive genes, associated with chromatin remodelling, DNAreplication, and DNArepair factors. A structural analysis of its bromodomain and subsequent investigations demonstrate that histone acetylation guides ATAD2 to chromatin, resulting in an overall increase of chromatin accessibility and histone dynamics, which is required for the proper activity of the highly expressed gene fraction of the genome. While in exponentially growing cells Atad2 appears dispensable for cell growth, in differentiating ES cells Atad2 becomes critical in sustaining specific gene expression programmes, controlling proliferation and differentiation. Altogether, this work defines Atad2 as a facilitator of general chromatin-templated activities such as transcription.