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Nature cell biology

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

Sidharth Sirdeshmukh

Research Associate, Dewpoint

NANOG is a transcription factor that can reestablish ground-state pluripotency in stem cells. The authors of this paper sought to investigate the LLPS dynamics that resulted from amino acid-level differences in NANOG c-termini, that may drive this effect. Changing all tryptophans to alanines (WT to W8A) resulted in smaller monomeric assemblies of NANOG, which was not favorable for droplet formation. Additionally, FRAP experiments confirmed that these larger WT assemblies recover from photobleaching more slowly than W8A. CHIP-seq experiments show that these amino acid changes influence the regions of chromatin DNA recognized by WT and W8A, which connects these findings to the actual biology of pluripotency control. From this paper it is worth considering whether a similar strategy of systematically substituting amino acids in c-termini of other core transcription factors (ie. OCT4, SOX2), or other proteins with amyloid-like behaviors, would deliver favorable LLPS events, and subsequently unlock the doors to multi-factor ESC fate control.