Three speeds of gene repositioning

Yeast use at least three different strategies to regulate how transcription factors position genes within the nucleus, Randise-Hinchliff et al. reveal.

In budding yeast, many genes are recruited to nuclear pore complexes when they are induced, potentially hastening the export of transcribed mRNAs into the cytoplasm. Repositioning can be mediated by transcription factors that bind to specific sites—called DNA zip codes—within the genes’ promoters. How cells regulate gene positioning remains unknown, however.

The transcription factor Put3 binds to a zip code in the promoter of INO1 and moves this gene to the nuclear periphery when it is induced in response to inositol starvation. Randise-Hinchliff et al. found that, in the presence of inositol, transcriptional repressors prevent Put3 from binding to INO1’s zip code by recruiting the histone deacetylase Rpd3(L), which presumably alters the promoter’s chromatin structure.

In contrast, the transcription factor Ste12 binds constitutively to the promoter of PRM1, and yet, the researchers found, it only moves this gene to the nuclear periphery in the presence of mating pheromone. The pheromone induces a MAP kinase signaling cascade that results in the phosphorylation and dissociation of a Ste12 inhibitor called Dig2, allowing PRM1 repositioning.

Finally, Randise-Hinchliff et al. found that the transcription factor Gcn4 increases HIS4 targeting to the nuclear periphery when its abundance—and thus its occupancy of the HIS4 promoter—increases in response to amino acid starvation.

Senior author Jason Brickner says that the different regulatory strategies allow cells to control gene positioning over different time scales; chromatin alterations and INO1 repositioning are relatively slow, whereas MAP kinase signaling and PRM1 targeting occur much faster. Changes in Gcn4 abundance, on the other hand, can fine-tune HIS4’s nuclear position over intermediate time scales.