Seminars Details

12.04.2021

Virtual Seminar: From sequence to space and time in single-cell genomics

Steffen Rulands; Group leader at the Max Planck Institute for the Physics of Complex Systems

Recent breakthroughs in single-cell genomics allow probing molecular states of cells with unprecedented detail along the DNA sequence. Biological function relies, however, on emergent processes in the three-dimensional space of the nucleus, such as phase separation phenomena. In this talk, I will show how such emergent processes in space and time can be inferred from linear sequencing experiments. We use single-cell multi-omics sequencing to develop a theoretical framework to map epigenome profiling along the DNA sequence onto a description of mesoscopic phenomena in space and time. Drawing on scNMT-seq in vitro and in vivo we exemplify our approach by showing how DNA methylation patterns of the embryonic genome are dynamically established through the interplay between DNA methylation and changes to DNA topology. This feedback determines genome-scale DNA methylation rates and leads to the formation of 30-40nm sized condensates of methylated DNA. Using this framework, we identify methylation structures preceding transcriptional changes at the exit from pluripotency. By combining novel methods from theoretical physics with single-cell sequencing our work overcomes a conceptual limitation of genomics.