The capability to control the progression of the cell cycle, including the means to enter into a stable non-proliferative state, is essential for eukaryotic unicellular and multicellular organisms. A quiescent state similar to G0 of higher eukaryotes can be induced by nitrogen starvation of the fission yeast model organism Schizosaccharomyces pombe. Using high-resolution tiling arrays for genome-wide transcriptional profiling we explore the early transcriptional reprogramming on the route to quiescence. Furthermore, we demonstrate that cells carrying a mutation in the high mobility group (HMG) box of the histone lysine demethylase spLsd1 fail to acquire characteristics of quiescent cells and rapidly lose viability under nitrogen-starved conditions. Since no such defect is seen as a result of catalytic inactivation, the HMG domain of spLsd1 seems to confer a function to the protein that is independent of the histone demethylase activity. We show that the HMG domain of spLsd1 is required for transcriptional activation and repression of a large set of genes, both during vegetative growth and on the route to quiescence. We also confirm that spLsd1 is a repressor of antisense transcription, and that this function is at least partially dependent on the HMG domain of the protein.