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

Abu Alhaija A. A., Lone I. N., Ozkuru Sekeroglu E., Batur T., Angelov D., Dimitrov S., ...Daha Fazla

FEBS Open Bio, cilt.14, sa.2, ss.309-321, 2024 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 14 Sayı: 2
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1002/2211-5463.13750
  • Dergi Adı: FEBS Open Bio
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.309-321
  • Anahtar Kelimeler: cellular model, CRISPR/Cas9, H1.4, linker histones, mES cells, Rahman syndrome
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

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.