Details

Autor(en) / Beteiligte

• Choi, Kyoung-Jae
• Quan, My Diem
• Qi, Chuangye
• Lee, Joo-Hyung
• Tsoi, Phoebe S.
• Zahabiyon, Mahla
• Bajic, Aleksandar
• Hu, Liya
• Prasad, B. V. Venkataram
• Liao, Shih-Chu Jeff
• Li, Wenbo
• Ferreon, Allan Chris M.
• Ferreon, Josephine C.

Titel

NANOG prion-like assembly mediates DNA bridging to facilitate chromatin reorganization and activation of pluripotency

Ist Teil von

• Nature cell biology, 2022-05, Vol.24 (5), p.737-747

Erscheinungsjahr

2022

Beschreibungen/Notizen

• Abstract Human NANOG expression resets stem cells to ground-state pluripotency. Here we identify the unique features of human NANOG that relate to its dose-sensitive function as a master transcription factor. NANOG is largely disordered, with a C-terminal prion-like domain that phase-transitions to gel-like condensates. Full-length NANOG readily forms higher-order oligomers at low nanomolar concentrations, orders of magnitude lower than typical amyloids. Using single-molecule Förster resonance energy transfer and fluorescence cross-correlation techniques, we show that NANOG oligomerization is essential for bridging DNA elements in vitro. Using chromatin immunoprecipitation sequencing and Hi-C 3.0 in cells, we validate that NANOG prion-like domain assembly is essential for specific DNA recognition and distant chromatin interactions. Our results provide a physical basis for the indispensable role of NANOG in shaping the pluripotent genome. NANOG’s unique ability to form prion-like assemblies could provide a cooperative and concerted DNA bridging mechanism that is essential for chromatin reorganization and dose-sensitive activation of ground-state pluripotency.