Arid4b physically interacts with Tfap2c in mouse embryonic stem cells

Keskin E. G., Huang J., TERZİ ÇİZMECİOĞLU N.

TURKISH JOURNAL OF BIOLOGY, cilt.45, sa.2, ss.162-170, 2021 (SCI-Expanded) identifier identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 45 Sayı: 2
  • Basım Tarihi: 2021
  • Doi Numarası: 10.3906/biy-2010-67
  • Dergi Adı: TURKISH JOURNAL OF BIOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Veterinary Science Database, TR DİZİN (ULAKBİM)
  • Sayfa Sayıları: ss.162-170
  • Anahtar Kelimeler: Chromatin, epigenetics, embryonic stem cell, lineage commitment, transcription factor, TRANSCRIPTION FACTORS, SUPER-ENHANCERS, PLURIPOTENCY, CHROMATIN, IDENTITY
  • Orta Doğu Teknik Üniversitesi Adresli: Evet

Özet

Precise regulation of gene expression is required for embryonic stem cell (ESC) differentiation. Transcription factor (TF) networks coordinate the balance of pluripotency and differentiation in response to extracellular and intracellular signals. Chromatin factors work alongside TFs to achieve timely regulation of gene expression for differentiation process. Our previous studies showed that a member of the Sin3a corepressor complex, Arid4b, is critical for proper mouse ESC differentiation into mesoderm and endoderm. We found elevated histone 3 lysine 27 acetylation (H3K27Ac) in a subset of genomic loci in meso/endoderm directed arid4b. cells, coincident with their derepression. We reasoned that Sin3a complex may be required for the suppression of these genes during differentiation. To identify TFs that might cooperate with Arid4b for this function, we found consensus TF binding sequences enriched in H3K27Ac elevated regions in arid4b. cells. Of these candidate TFs, we validated expression of Bach1, Ddit3, Prrx2, Znf354c and Tfap2c in mESCs. We then demonstrated a physical interaction between Arid4b and Tfap2c in mESCs using endogenous coimmunoprecipitation and proximity ligation assay experiments. Our results point to a role of Arid4b in the Sin3a complex in repression of a subset of Tfap2cregulated genes during meso/endoderm differentiation.