Publication: Development of a mouse embryonic stem cell model for investigating the functions of the linker histone H1-4
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KU Authors
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Abu Alhaija, A.A.
Lone, I.N., Ozkuru Sekeroglu, E., Batur, T., Angelov, D.
Dimitrov, S.
Hamiche, A.
Yagci, T.
Alotaibi, H.
Diril, M.K.
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Abstract
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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Wiley
Subject
Biochemistry and molecular biology
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FEBS Open Bio
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DOI
10.1002/2211-5463.13750