HMGN5, an RNA and Nucleosome binding protein required for chromatin de-condensation and gene activation

The packaging of DNA into chromatin and its compaction within cells renders the underlying DNA template un-accessible for processes like transcription, replication and repair. Active mechanisms as chromatin modifying activities or the association with non-coding RNAs can de-condense chromatin, rendering it accessible for the DNA dependent processes. High mobility group proteins (HMG) are small architectural chromatin proteins that were shown to contribute to the regulation of chromatin accessibility and condensation. Here we show that HMGN5, a member of the HMGN family is capable to de-compact chromatin and to activate gene expression. We identified and characterized a novel RNA binding domain within HMGN5 that overlaps with its nucleosome binding domain (NBD). HMGN5 binds exclusively to nucleosomes or RNA, suggesting a switching mechanism and different functionalities depending on its binding partner. For this we show that HMGN5 is bound to regulatory regions of the genes that it tends to activate and also is found on the primary transcript of these genes. The results suggest that HMGN5 is switching from the chromatin binding to the RNA binding state after gene activation, potentially improving RNA synthesis. Furthermore, HMGN5 co-localizes and directly interacts with CTCF, suggesting a cooperative role of both proteins in organizing higher order structures of chromatin and active chromatin domains.