GAS41 modulates ferroptosis by anchoring NRF2 on chromatin.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38514704.
- Also identified by DOI 10.1038/s41467-024-46857-w and PMC identifier 10957913.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
YEATS domain-containing protein GAS41 is a histone reader and oncogene. Here, through genome-wide CRISPR-Cas9 screenings, we identify GAS41 as a repressor of ferroptosis. GAS41 interacts with NRF2 and is critical for NRF2 to activate its targets such as SLC7A11 for modulating ferroptosis. By recognizing the H3K27-acetylation (H3K27-ac) marker, GAS41 is recruited to the SLC7A11 promoter, independent of NRF2 binding. By bridging the interaction between NRF2 and the H3K27-ac marker, GAS41 acts as an anchor for NRF2 on chromatin in a promoter-specific manner for transcriptional activation. Moreover, the GAS41-mediated effect on ferroptosis contributes to its oncogenic role in vivo. These data demonstrate that GAS41 is a target for modulating tumor growth through ferroptosis. Our study reveals a mechanism for GAS41-mediated regulation in transcription by anchoring NRF2 on chromatin, and provides a model in which the DNA binding activity on chromatin by transcriptional factors (NRF2) can be directly regulated by histone markers (H3K27-ac).
Medical subject headings
- Histones
- Ferroptosis