Review article

Transcriptional condensates as kinetic filters for temporal control of gene expression

Where this started

Cell signaling is rarely constant. Pathways such as ERK, NF-κB, and p53 transmit information through pulses, oscillations, signal duration, and amplitude. Yet transcriptional regulation is often described spatially, with emphasis on which factors assemble at enhancers and promoters.

This left us with a different question.

Could the time required to assemble and dissolve transcriptional condensates influence how cells interpret dynamic signals?

A different way to consider transcriptional condensates

Transcriptional condensates are commonly studied as spatial organizers that concentrate transcription factors, cofactors, and RNA polymerase II at regulatory regions.

However, these assemblies are also dynamic. They form only after specific molecular thresholds are crossed, exchange components with their surroundings, persist for variable periods, and eventually dissolve.

This means that their kinetics may be just as important as their location.

The kinetic-filter model

In our review, we propose a kinetic-filter model based on four interconnected properties.

• Nucleation thresholds determine whether a signal is sufficient to initiate condensate formation.
• Finite assembly and molecular exchange kinetics determine how quickly the system responds.
• Condensate persistence may maintain a transcriptionally competent state after the initiating signal changes.
• Regulated dissolution resets the system and limits continued transcription.

Under this model, a brief signal may disappear before a stable condensate can form. A sustained or repeatedly delivered signal may maintain the conditions required for nucleation and assembly.

Condensates could therefore attenuate rapid fluctuations while transmitting signals that persist long enough to support organized transcriptional activity. Their persistence after signal withdrawal could also provide a form of short-term molecular memory.

What this could mean for transcription

If condensates operate as kinetic filters, their dynamics may influence transcriptional bursting.

A lower nucleation barrier could increase the probability that a gene enters an active state. Greater condensate persistence could prolong transcriptional bursts, while regulated dissolution could terminate transcription and restore responsiveness to subsequent signals.

Gene expression may therefore depend not only on whether regulatory molecules are present, but also on whether they remain present long enough for the transcriptional machinery to assemble and respond.

What remains unresolved

The complete causal sequence linking a defined temporal signal, condensate kinetics, and endogenous nascent transcription has not yet been demonstrated.

Thresholds, persistence, adaptation, and transcriptional bursting can also arise through cooperative transcription factor binding, chromatin regulation, promoter-state switching, RNA polymerase II pausing, and feedback circuits.

For this reason, we present transcriptional condensates as candidate kinetic intermediaries rather than universal temporal decoders.

Where this leads

The decisive experiments must measure temporal signaling inputs, condensate dynamics, and nascent transcription simultaneously in the same cells.

They must also selectively alter condensate formation delay, molecular exchange, persistence, or dissolution while controlling for protein abundance, DNA binding, chromatin accessibility, catalytic activity, and upstream signaling.

The question is no longer simply whether transcriptional condensates form.

It is whether their kinetics determine which signals become gene expression.

Reference

Sailis AB. Transcriptional condensates as kinetic filters for temporal control of gene expression. Gene Reports. 2026. https://doi.org/10.1016/j.genrep.2026.102599

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