# Phase-separated NDF−FACT condensates facilitate transcription elongation on chromatin

## TL;DR

The study shows that phase-separated NDF-FACT condensates help RNA polymerase II overcome chromatin barriers during transcription, preserving chromatin structure in human stem cells.

## Contribution

The study reveals that phase-separated NDF−FACT condensates enhance transcription elongation by creating a specialized biochemical environment.

## Key findings

- NDF−FACT condensates increase transcription efficiency about 20-fold compared to FACT alone.
- These condensates promote nucleosome disassembly while preserving chromatin integrity by retaining histones.
- Disruption of NDF−FACT condensates causes genome-wide transcriptional defects and chromatin instability in human stem cells.

## Abstract

How the facilitates chromatin transcription (FACT) complex enables RNA polymerase II to overcome chromatin barriers in cells remains poorly understood—especially given the limited direct interactions of FACT with polymerases, DNA or nucleosomes. Here we demonstrate that phase separation, mediated by nucleosome destabilizing factor (NDF), is a key mechanism enabling the function of FACT during transcription elongation. Through biochemical and single-molecule assays, we found that NDF−FACT condensates create specialized biochemical environments that enhance transcription efficiency approximately 20-fold compared with FACT alone. These dynamic condensates form on transcribing RNA polymerase II and travel along chromatin, where they promote efficient nucleosome disassembly at barriers while retaining histones on DNA to preserve chromatin integrity. In human stem cells, disruption of these condensates leads to genome-wide transcriptional defects and chromatin instability, mirroring the effects of FACT depletion. By showing that phase separation enhances FACT function during transcription elongation, our study reveals a key mechanism that preserves chromatin integrity and transcriptional homeostasis in human stem cells.

Li, Burgos-Bravo and colleagues report that NDF phase separation regulates FACT condensation, which enhances transcription by generating a localized biochemical environment that promotes nucleosome disassembly while preserving chromatin integrity by retaining histones.