Pervasive lncRNA binding by epigenetic modifying complexes - The challenges ahead

Epigenetic modifying factors are fundamental regulators of chromatin structure and gene expression during development and differentiation through the induction of chemical modifications on histones, DNA or via remodeling of the chromatin structure. Protein complexes involved in these three processes contain non-canonical RNA-binding components that interact with long non-coding RNAs, in many cases in the absence of any sequence or structural signatures. However, there is growing evidence of the role of such protein-lncRNA interactions in the regulation of the epigenetic landscape in vivo. This review summarizes the growing number of epigenetic modifying factors described to interact with lncRNAs in mouse and human, and then discusses the challenges that lay ahead in understanding lncRNAs as part of the intricate networks of epigenetic regulation. A combination of protein and RNA-centric approaches is required for this purpose. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa.