Amphiphiles formed from synthetic DNA-nanomotifs mimic the step-wise dispersal of transcriptional clusters in the cell nucleus

Abstract

Stem cells exhibit prominent clusters controlling the transcription of genes into RNA. These clusters form by a phase-separation mechanism, and their size and shape are controlled via an amphiphilic effect of transcribed genes. Here, we construct amphiphile-nanomotifs purely from DNA, and achieve similar size and shape control for phase-separated droplets formed from fully synthetic, self-interacting DNA-nanomotifs. Low amphiphile concentrations induce rounding of droplets, followed by splitting and, ultimately, full dispersal at higher concentrations. Super-resolution microscopy data obtained from zebrafish embryo stem cells reveal a comparable transition for transcriptional clusters with increasing transcription levels. Brownian dynamics and lattice simulations further confirm that addition of amphiphilic particles is sufficient to explain the observed changes in shape and size. Our work reproduces key aspects of the complex organization of transcription in biological cells using relatively simple, DNA sequence-programmable nanostructures, opening novel ways to control mesoscopic organization of synthetic nanomaterials. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/525851v2_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@1a8cc4borg.highwire.dtl.DTLVardef@fc6651org.highwire.dtl.DTLVardef@a17c74org.highwire.dtl.DTLVardef@1f1cf14_HPS_FORMAT_FIGEXP M_FIG C_FIG