Periodic epi-organization of the yeast genome revealed by the distribution of promoter sites.

The organization of transcription within the eukaryotic nucleus may be expected to both depend on and determine the structure of the chromosomes. This study shows that, in yeast, genes that are controlled by the same sequence-specific transcription factor tend to be regularly spaced along the chromosome arms; a similar period characterizes the spacing of origins of replication, although periodicity is less pronounced. The same period is found for most transcription factors within a chromosome arm. However, different periods are observed for different chromosome arms, making it unlikely that periodicity is caused by dedicated scaffolding proteins. Such regularities are consistent with a genome-wide loop model of chromosomes, in which coregulated genes tend to dynamically colocalize in 3D. This colocalization may also involve co-regulated genes belonging to different chromosomes, as suggested by partial conservation of the respective positioning of different transcription factors around the loops. Thus, binding at genuine regulatory sites on DNA would be optimized by locally increasing the concentration of multimeric transcription factors. In this model, self-organization of transcriptional initiation plays a major role in the functional nuclear architecture.