Fiche publication
Date publication
mai 2026
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr HAMICHE Ali
Tous les auteurs :
Boopathi R, Garcia-Saez I, Turunç S, Lone IN, Kumar A, Abu Alhaija AA, Hayes JJ, Bednar J, Diril MK, Iliev D, Gospodinov A, Le Roy A, Skoufias D, Angelov D, Hamiche A, Kale S, Dimitrov S, Petosa C
Lien Pubmed
Résumé
Rahman syndrome is a rare developmental disorder caused by frameshift mutations in linker histone H1.4 that produce a truncated carboxy-terminal domain with reduced positive charge. We investigated the effects of a disease-associated mutation on chromatin structure and dynamics, focusing on H1.4-bound nucleosomes and hexanucleosomal arrays. We report that this mutation induces a more extended and flexible array conformation, characterized by enhanced linker DNA accessibility and an inability to form compact, regularly stacked nucleosome structures. Notably, mutant H1.4-bound arrays show a reduced capacity to undergo liquid-liquid and liquid-solid phase separation, closely resembling linker histone-free arrays. Molecular dynamics simulations corroborated by fluorescence resonance energy transfer measurements indicate that the mutated carboxy-terminal domain interacts with a shorter linker DNA segment, resulting in a more open nucleosome conformation. Consistent with these structural changes, the mutation significantly enhances H1.4 mobility within cell nuclei, reflecting a weaker chromatin association. The combined data suggest that Rahman syndrome-associated mutations promote an aberrantly relaxed chromatin state, potentially leading to the dysregulation of gene expression that may drive disease pathology. These findings underscore the essential role of the carboxy-terminal domain in chromatin compaction and provide mechanistic insights into the molecular etiology of Rahman syndrome.
Référence
Nat Commun. 2026 05 22;:
