Transcription factor condensates and signaling driven transcription

Abstract

Transcription Factor (TF) condensates are a heterogenous mix of RNA, DNA, and multiple co-factor proteins capable of modulating the transcriptional response of the cell. The dynamic nature and the spatial location of TF-condensates in the 3D nuclear space is believed to provide a fast response, which is on the same pace as the signaling cascade and yet ever-so-specific in the crowded environment of the nucleus. However, the current understanding of how TF-condensates can achieve these feet so quickly and efficiently is still unclear. In this review, we draw parallels with other protein condensates and share our speculations on how the nucleus uses these TF-condensates to achieve high transcriptional specificity and fidelity. We discuss the various constituents of TF-condensates, their properties, and the known and unknown functions of TF-condensates with a particular focus on steroid signaling-induced transcriptional programs.

Phase Separation as a Driver of Stem Cell Organization and Function during Development

“…Disordered AD sequences resemble those found in other protein condensates and are typified by an abundance of acidic residues [57,58]. Not surprisingly then, much evidence has now emerged spotlighting the capacity for condensation of TF complexes, which typically contain DNA and RNA along with co-regulatory proteins [59]. This phenomenon was first described to involve TF complexes associated at super-enhancers, genomic regions that assemble in a cooperative manner to ensure robust gene expression, notably including those involved in stem cell fate and identity [60,61].…”

Transcriptional condensates: a blessing or a curse for gene regulation?

“…A recent report shows that the charge patterns of IDRs define the selective partitioning of biomolecules into different condensates, with possible functional consequences 37 , including the segregation of different transcriptional programs into specific transcriptional condensates 38 . Moreover, different types of transcriptional condensates seem to control several steps of gene activation, including the formation of preinitiation complexes, transcriptional pausing and elongation, super-enhancer clustering, and mRNA splicing and processing 39,40 .…”

Selective phase separation of transcription factors is driven by orthogonal molecular grammar

“…In this work we aim to identify the molecular interactions that drive selective condensate formation, by focusing on a range of transcription factors from three different transcription families (FET, SP/KLF and HNF). It has been hypothesized that the selectivity of TFs is caused by differential phase separation propensities [22, 24, 43, 44]. Here we test this hypothesis by analyzing ternary phase diagrams of six TFs that all undergo PS to form condensates on their own under biological conditions [22, 24, 45].…”