# NCOA1, NCOA2 and NCOA3 identified as histone succinyltransferases in mammalian cell studies

- Published: 2026-11-14 06:26 UTC
- Section: Life & Health › Biology & biochemistry
- Tags: histone succinylation, histone succinyltransferase, NCOA1 NCOA2 NCOA3, nuclear receptor coactivators, Mediator complex, gene promoters, global transcription, embryonic stem cells, phase separation, lysine acylation
- URL: https://realtech.media/news/rt-707921c99f78fb1cfe0d28a8_ncoa1_ncoa2_and/

**Authors report that three nuclear receptor coactivators catalyze bulk histone succinylation, and that this mark helps the Mediator complex bind promoters in cell experiments.**

![NCOA1, NCOA2 and NCOA3 identified as histone succinyltransferases in mammalian cell studies](https://realtech.media/media/2026/11/1bcb036f28a6601a.jpg)
*Syed Sajidul Islam, Wikimedia Commons, CC BY-SA 4.0*

Researchers report that the nuclear receptor coactivators NCOA1, NCOA2 and NCOA3 act as histone succinyltransferases (HSTs) and are responsible for bulk histone succinylation in mammalian cells, according to a paper available via doi.org [1]. Histone succinylation is a conserved lysine acylation, but its mechanism and its role in transcription had remained unclear [1]. The work combines in vitro assays with genome-wide profiling in cancer cells and embryonic stem cells.

## NCOA proteins as succinyltransferases

Classic acetyltransferases such as CBP/p300 possess several acyltransferase activities. NCOA1/2/3, by contrast, exhibit only HST activity [1]. The authors report that the proteins drive the formation of phase-separation condensates through this activity [1].

In mouse embryonic stem cells lacking Ncoa1 and Ncoa2, rapid targeted degradation of NCOA3 caused a marked, immediate loss of bulk histone succinylation. It was accompanied by a widespread decline in global transcriptional activity [1].

## Mediator as a reader of the mark

In vitro binding assays identified the Mediator complex as a specific reader of succinylated histone tail peptides and nucleosomes [1]. Epigenome profiling, based on ChIP-seq, CUT&Tag-seq, RNA-seq and TT-seq data, showed that histone succinylation catalyzed by NCOA1/2/3 is highly enriched at gene promoters [1]. According to the authors, this mark is essential for the association of the Mediator complex with promoters [1].

The NCOA family of HSTs is also critically important for global transcriptional activity in both cancer cells and embryonic stem cells [1]. The authors conclude that NCOA1/2/3 are unique histone succinyltransferases and that histone succinylation is a critical regulator of Mediator promoter association and of global transcriptional activation [1].

The results were obtained in vitro and in cultured mammalian cells. The material contains no data on animals or patients.

## Sources

1. [doi.org](https://doi.org/10.1038/s41589-026-02379-8)
2. [bioengineer.org](https://bioengineer.org/nuclear-receptor-coactivators-ncoa1-ncoa2-and-ncoa3-catalyze-histone-succinylation)

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Source: RealTech, realtech.media — https://realtech.media/news/rt-707921c99f78fb1cfe0d28a8_ncoa1_ncoa2_and/