Intrinsically Disordered Regions Direct Transcription Factor In Vivo Binding Specificity.

Transcription factors (TFs) that bind common DNA motifs in vitro occupy distinct sets of promoters in vivo, raising the question of how binding specificity is achieved. TFs are enriched with intrinsically disordered regions (IDRs). Such regions commonly form promiscuous interactions, yet their unique properties might also benefit specific binding-site selection.

Transcription Factor Binding to Replicated DNA.

Genome replication perturbs the DNA regulatory environment by displacing DNA-bound proteins, replacing nucleosomes, and introducing dosage imbalance between regions replicating at different S-phase stages. Recently, we showed that these effects are integrated to maintain transcription homeostasis: replicated genes increase in dosage, but their expression remains stable due to replication-dependent epigenetic changes that suppress transcription. Here, we examine whether reduced transcription from replicated DNA results from limited accessibility to regulatory factors by measuring the time-resolved binding of RNA polymerase II (Pol II) and specific transcription factors (TFs) to DNA during S phase in budding yeast.

Resolving noise-control conflict by gene duplication.

Gene duplication promotes adaptive evolution in two main ways: allowing one duplicate to evolve a new function and splitting ancestral functions between the duplicates. The second scenario may resolve adaptive conflicts that can rise when one gene performs different functions. In an apparent departure from both scenarios, low-expressing transcription factor (TF) duplicates commonly bind to the same DNA motifs and act in overlapping conditions.

Bursty gene expression in the intact mammalian liver.

Bursts of nascent mRNA have been shown to lead to substantial cell-cell variation in unicellular organisms, facilitating diverse responses to environmental challenges. It is unknown whether similar bursts and gene-expression noise occur in mammalian tissues. To address this, we combine single molecule transcript counting with dual-color labeling and quantification of nascent mRNA to characterize promoter states, transcription rates, and transcript lifetimes in the intact mouse liver.