The DNase I hypersensitive sites (DHSs) of chromatin constitute one of the best landmarks of eukaryotic genes that are poised and/or activated for transcription. For over 35 years, the high-mobility group nucleosome-binding chromosomal proteins HMGN1 and HMGN2 have been shown to play a role in the establishment of these chromatin-accessible domains at transcriptional regulatory elements, namely promoters and enhancers. The critical presence of HMGNs at enhancers, as highlighted by a recent publication, suggests a role for them in the structural and functional fine-tuning of the DHSs in vertebrates. As we review here, while preferentially out-competing histone H1 binding and invading neighbor nucleosomes, HMGNs may also modulate histone H3 at serine 10 (H3S10ph), which plays an important role in enhancer function and transcriptional initiation.
