Dresden 2017 – scientific programme
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BP: Fachverband Biologische Physik
BP 32: Posters - DNA/RNA
BP 32.2: Poster
Tuesday, March 21, 2017, 14:00–16:00, P2-OG1
Transcription by RNA polymerase II establishes DNA microstructure — •Lennart Hilbert1,2,3, Yuko Sato4, Alf Honigmann2, Frank Jülicher3, Hiroshi Kimura4, Nadine L Vastenhouw2, and Vasily Zaburdaev3,1 — 1Center for Systems Biology Dresden — 2MPI Molecular Cell Biology and Genetics — 3MPI Physics of Complex Systems — 4Tokyo Institute of Technology
In interphase cell nuclei, DNA forms a microstructure of interspersed high concentration and low concentration regions. Transcription of DNA is carried out by RNA Polymerase II (Pol II) in low DNA density regions. While this organization reflects a need to unfold DNA for Pol II access, the causal origin of this spatial organization remains unclear. Here, we investigate if and how transcribing Pol II organizes DNA. Using zebrafish embryo cells, we found that Pol II needs to fill nuclei with RNA to induce segregation of DNA and RNA into a fine microstructure of mutually exclusive regions. We observed that the global DNA/RNA microstructure collapsed into a coarse pattern upon transcription inhibition. The microstructure originated from individual transcription sites, which locally displaced DNA by an RNA-rich region upon transcription activation. Our experimental results can be recapitulated in a simulated microemulsion. Here, the accumulation of nuclear RNA induces a global phase separation of DNA and RNA. Transcribing Pol II - tethered to both DNA and RNA - acted as a bivalent copolymer, locally dispersing DNA in the RNA phase. In summary, transcription by Pol II appears as a major driver of nuclear organization, which can be understood in the framework of phase separation.