Rational cell fate engineering through chromatin dynamics [CUT&TAG]

Mechanism controlling cell fate remains elusive. Chromatin remodeling complex interacts with transcription factors to colocalize across the genome and regulate region-specific epigenetic environment. Here, we propose an engineering approach for controlling cell fate through chromatin closing and opening. We utilize chromatin remodeling complex, BAF, known to activate gene expression by opening chromatin loci. By grafting BAF interacting motifs onto Nanog, we show that engineering factors could promote somatic cell reprogramming with Oct4. Furthermore, mutation on the interacting motifs render iPSC generation. The syntactic factors facilitate cell fate transition by recruiting BAF complex to modulate chromatin accessibility and reorganize cell state specific enhancers. Our findings reveal alternative methods to control cell fate by manipulating chromatin accessibility. Overall design: CUT&Tag analysis was performed in reprogramming intermediates of day 5 to map Nanog, Smarca4, H3K27ac and H3K4me binding sites.