# Twelve O-GlcNAc sites in BRD4 disordered region tune condensate fluidity and gene expression in cells

- Published: 2026-11-06 04:54 UTC
- Section: Life & Health › Biology & biochemistry
- Tags: O-GlcNAc clusters, BRD4 condensates, liquid-liquid phase separation, intrinsically disordered regions, transcriptional condensates, YTHDC1, super-enhancers, post-translational modifications, O-GlcNAcome, Protein & Cell
- URL: https://realtech.media/news/rt-6a53e64fd7f3baac9d69f460_twelve_o_glcnac/

**Authors of a Protein & Cell study found that O-GlcNAc sites cluster in disordered regions of transcription-related proteins; in BRD4, the modification makes condensates smaller and more fluid.**

![Twelve O-GlcNAc sites in BRD4 disordered region tune condensate fluidity and gene expression in cells](https://sgzwpqqelzmajkcubgkl.supabase.co/storage/v1/object/public/rt-media/2026/11/2e8c047461d08b47.jpg)
*Erin Rod, Wikimedia Commons, CC BY 4.0*

A research group reported in Protein & Cell that O-linked β-N-acetylglucosamine (O-GlcNAc) modifications form clusters in intrinsically disordered regions (IDRs) of transcription-related proteins and regulate liquid-liquid phase separation (LLPS). The work was released on 5 November 2026 through Higher Education Press. BRD4 (Bromodomain-containing protein 4) showed this pattern most prominently, with twelve clustered O-GlcNAc sites in its C-terminal IDR [1].

## O-GlcNAc clusters and phase separation

Post-translational modifications are known to regulate LLPS, which organizes biomolecular condensates, but general rules for O-GlcNAc had not been defined. The authors performed a proteome-wide analysis of the human O-GlcNAcome. According to their data, O-GlcNAc sites are enriched in IDRs and often form dense groups, termed O-GlcNAc clusters [1].

These clusters were strongly associated with phase-separating proteins, particularly transcriptional regulators. Proteins containing clusters had a significantly higher phase-separation propensity. Similar regulatory effects were observed in several other transcription-associated condensate proteins [1].

## BRD4 condensates and transcription

In BRD4, the twelve sites in the C-terminal IDR acted cooperatively rather than individually. The modification decreased condensate size and increased fluidity, both in vitro and in cells [1].

Multi-omics analyses examined what happens when O-GlcNAc is removed. BRD4 binding strengthened at active enhancers, including super-enhancers. LLPS-mediated recruitment of transcriptional cofactors, including YTHDC1, increased as well [1].

This was accompanied by elevated expression of genes linked to the cell cycle, DNA damage repair and cell proliferation [1].

The authors conclude that O-GlcNAc clusters regulate the material properties of condensates and transcriptional outcomes. In their interpretation, post-translational modifications fine-tune the molecular grammar of biomolecular condensates, and several individually weak glycosylation events act together to control protein assembly, chromatin engagement and gene expression [1].

The study is experimental: the data come from in vitro assays, cultured cells and omics analyses. The article is published in Protein & Cell (DOI 10.1093/procel/pwag053).

## Sources

1. [Protein & Cell](https://doi.org/10.1093/procel/pwag053)
2. [EurekAlert](https://www.eurekalert.org/news-releases/1150628)

---

Source: RealTech, realtech.media — https://realtech.media/news/rt-6a53e64fd7f3baac9d69f460_twelve_o_glcnac/