
メチオニン欠乏時に転写因子Met4とその共活性化因子Met32が核内で凝集体を形成し、標的遺伝子の3次元的クラスター化を促進することで、それらの遺伝子発現を強化する。


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Some transcription factors (TFs) can form liquid-liquid phase separated (LLPS) condensates. However, the functions of these TF condensates in 3D genome organization and gene regulation remain elusive. In response to methionine (met) starvation, budding yeast TF Met4 and a few co-activators, including Met32, induce a set of genes involved in met biosynthesis. Here, we show that the endogenous Met4 and Met32 form co-localized puncta-like structures in yeast nuclei upon met depletion. Recombinant Met4 and Met32 form mixed droplets with LLPS properties in vitro . In relation to chromatin, Met4 puncta co-localize with target genes, and at least a subset of these target genes are clustered in 3D in a Met4-dependent manner. A MET3pr -GFP reporter inserted near several native Met4 binding sites becomes co-localized with Met4 puncta and displays enhanced transcriptional activity. A Met4 variant with a partial truncation of an intrinsically disordered region (IDR) shows less puncta formation, and this mutant selectively reduces the reporter activity near Met4 binding sites to the basal level. Overall, these results support a model where Met4 and co-activators form condensates to bring multiple target genes into a vicinity with higher local TF concentrations, which facilitates a strong response to methionine depletion.

### Competing Interest Statement

The authors have declared no competing interest.

Transcription Factor Condensates Mediate Clustering of MET Regulon and Enhancement in Gene Expression

メチオニン欠乏時に転写因子met4とその共活性化因子met32が形成する凝集体が-標的遺伝子のクラスター化と遺伝子発現の増強に寄与する


メチオニン欠乏時に転写因子Met4とその共活性化因子Met32が形成する凝集体が、標的遺伝子のクラスター化と遺伝子発現の増強に寄与する
