Transcriptional activation during cell reprogramming correlates with the formation of 3D open chromatin hubs

Marco Di Stefano (), Ralph Stadhouders, Irene Farabella, David Castillo, François Serra, Thomas Graf () and Marc A. Marti-Renom ()
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Marco Di Stefano: Barcelona Institute of Science and Technology (BIST)
Ralph Stadhouders: Barcelona Institute of Science and Technology (BIST)
Irene Farabella: Barcelona Institute of Science and Technology (BIST)
David Castillo: Barcelona Institute of Science and Technology (BIST)
François Serra: Barcelona Institute of Science and Technology (BIST)
Thomas Graf: Barcelona Institute of Science and Technology (BIST)
Marc A. Marti-Renom: Barcelona Institute of Science and Technology (BIST)

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract Chromosome structure is a crucial regulatory factor for a wide range of nuclear processes. Chromosome conformation capture (3C)-based experiments combined with computational modelling are pivotal for unveiling 3D chromosome structure. Here, we introduce TADdyn, a tool that integrates time-course 3C data, restraint-based modelling, and molecular dynamics to simulate the structural rearrangements of genomic loci in a completely data-driven way. We apply TADdyn on in situ Hi-C time-course experiments studying the reprogramming of murine B cells to pluripotent cells, and characterize the structural rearrangements that take place upon changes in the transcriptional state of 21 genomic loci of diverse expression dynamics. By measuring various structural and dynamical properties, we find that during gene activation, the transcription starting site contacts with open and active regions in 3D chromatin domains. We propose that these 3D hubs of open and active chromatin may constitute a general feature to trigger and maintain gene transcription.

Date: 2020
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DOI: 10.1038/s41467-020-16396-1

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