The organisation of chromatin is first discussed to conclude that nucleosomes play both structural and transcription-regulatory roles. The presence of nucleosomes makes difficult the access of transcriptional factors to their target sequences and the action of RNA polymerases. The histone post-translational modifications and nucleosome remodelling are first discussed, from a historical point of view, as mechanisms to remove the obstacles imposed by chromatin structure to transcription. Instead of reviewing the state of the art of the whole field, this review is centred on some open questions. First, some "non-classical" histone modifications, such as short-chain acylations other than acetylation, are considered to conclude that their relationship with the concentration of metabolic intermediaries might make of them a sensor of the physiological state of the cells. Then attention is paid to the interest of studying chromatin organisation and epigenetic marks at a single nucleosome level as a complement to genome-wide approaches. Finally, as a consequence of the above questions, the review focuses on the presence of multiple histone post-translational modifications on a single nucleosome. The methods to detect them and their meaning, with special emphasis on bivalent marks, are discussed.