Article Dans Une Revue FEBS Open Bio Année : 2024

Development of a mouse embryonic stem cell model for investigating the functions of the linker histone H1‐4

Imtiaz Nisar Lone
Elif Nur Firat Karalar
Muhammed Erdem Ercan
Tamer Yagci

Résumé

The 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.

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hal-04663219 , version 1 (26-07-2024)

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Abed Alkarem Abu Alhaija, Imtiaz Nisar Lone, Esin Ozkuru Sekeroglu, Tugce Batur, Dimitar Angelov, et al.. Development of a mouse embryonic stem cell model for investigating the functions of the linker histone H1‐4. FEBS Open Bio, 2024, 14 (2), pp.309 - 321. ⟨10.1002/2211-5463.13750⟩. ⟨hal-04663219⟩
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