Development of a mouse embryonic stem cell model for investigating the functions of the linker histone H1-4.
Fiche publication
Date publication
décembre 2023
Journal
FEBS open bio
Auteurs
Membres identifiés du Cancéropôle Est :
Dr HAMICHE Ali
Tous les auteurs :
Abu Alhaija AA, Lone IN, Ozkuru Sekeroglu E, Batur T, Angelov D, Dimitrov S, Hamiche A, Firat Karalar EN, Ercan ME, Yagci T, Alotaibi H, Diril MK
Lien Pubmed
Résumé
Linker histone H1 C-terminal domain (CTD) plays a pivotal role in chromatin condensation. De novo frameshift mutations within the CTD coding region of H1.4 have recently been reported to be associated with Rahman syndrome, a neurological disease that causes intellectual disability and overgrowth. To investigate the mechanisms and pathogenesis of Rahman syndrome, we developed a cellular model using murine embryonic stem cells (mESCs) and CRISPR/Cas9 genome engineering. Our engineered mES cells facilitate detailed investigations, such as H1-4 dynamics, immunoprecipitation, and nuclear localization; in addition, we tagged the mutant H1-4 with a photoactivatable GFP (PA-GFP) and an HA tag to facilitate pulldown assays. We anticipate that these engineered cells could also be used for the development of a mouse model to study the in vivo role of the H1-4 protein.
Mots clés
CRISPR/Cas9, H1.4, Rahman syndrome, cellular model, linker histones, mES cells
Référence
FEBS Open Bio. 2023 12 14;: