Only a small fraction of eukaryotic genomes encodes for proteins; the majority however, is non-coding DNA. Remarkably, even though these sequences lack protein-coding potential, they are transcriptionally active resulting in non-coding RNA molecules. It has become clear over the last decades that such non-coding RNA molecules or the act of their transcription, first neglected as a useless by-product of spontaneous RNA Polymerase II activity, can have biologically relevant functions. Bi-directional promoters, giving rise to transcription events in both directions, are the origin of a large fraction of non-coding transcription.
This thesis analyses the involvement of histone proteins H3 and H4 in the regulation of non-coding transcription initiation from bi-directional promoters. Furthermore, the presented results show how the accurate transcriptional termination of non-coding transcription events from bi-directional promoters is needed to prevent repression of downstream genes. The locus investigated in this thesis provides a great platform to analyse to what extent different non-coding sequences can substitute each other’s function. Lastly, the thesis provides an outlook on how to use the fundamental knowledge generated in this thesis when finding genetic diagnoses for people suffering malfunctions caused by changes in their non-coding DNA.