Multiomic screening platform uncovers the impact of histone mutations on chromatin and cell fate
expression leads to suppression of promoter-associated H3K4me3 and expansion of repressive H3K27me3 domains, resulting in increased KRAS signaling and gene expression programs associated with epithelial-to-mesenchymal transition. Together, this work provides a multiomic functional atlas of cancer-associated histone mutations, identifies structural and mechanistic principles governing chromatin reprogramming by oncohistones, and establishes CHANCLA as a modular platform for systematic discovery of mechanisms and vulnerabilities associated with these genetic lesions.
Authors
- Agata L. Patriotis (ORCID: https://orcid.org/0000-0002-8237-975X)
- Amy E. Keating (ORCID: https://orcid.org/0000-0003-4074-8980)
- Foster Birnbaum (ORCID: https://orcid.org/0000-0002-6062-2296)
- Leah Gates (ORCID: https://orcid.org/0000-0001-6850-8167)
- Margaret R. Brown (ORCID: https://orcid.org/0000-0002-0914-8496)
- Francisco J. Sánchez-Rivera
- Arianna Arroyo-Ortega
- Renée L. Barbosa
- Daniel Lee
- Yadira M. Soto-Feliciano (ORCID: https://orcid.org/0000-0001-5118-8478)
- Ziyang Ye
- Lijuan Feng
- Alireza Khademi
- Colin E. Fowler
Institutions
- Harvard University (US)
- Washington University in St. Louis (US)
- Precision for Medicine (United States) (US)
- Allen Institute (US)
- Decision Systems (United States) (US)
- University School (US)
- Koch Institute for Integrative Cancer Research At MIT (US)
- Case Western Reserve University (US)
- Massachusetts Institute of Technology (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-04-17
- DOI
- https://doi.org/10.64898/2026.04.14.718582
- Primary Topic
- Genomics and Chromatin Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Howard Hughes Medical Institute
- American Association for Cancer Research