New ultra-detailed imaging exposes the hidden structure and behavior of chromatin condensates — and hints at how their failures may drive di
"Six feet of human DNA crammed into a tiny nucleus relies on an elegant system of nucleosomes, fibers, and highly organized phase-separated condensates.
Scientists have now captured the most detailed images yet of how chromatin fibers and nucleosomes arrange themselves inside these droplet-like structures, revealing how molecular architecture determines condensate behavior."
"Inside every human cell, biology manages an extraordinary challenge: packing roughly six feet of DNA into a nucleus that is only about one-tenth the width of a human hair, all while keeping the genetic material fully functional.
To achieve this level of compression, DNA coils around proteins to form nucleosomes. These nucleosomes connect like beads on a string, creating long strands that fold into chromatin fibers. The fibers then compact even further to fit inside the nucleus.
For years, scientists did not know exactly how this final stage of compaction occurred. That changed in 2019, when HHMI Investigator Michael Rosen and his colleagues at UT Southwestern Medical Center showed that lab-made nucleosomes can gather into membrane-less droplets called condensates. They discovered that this occurs through phase separation – a process similar to oil droplets forming in water – which may mirror how chromatin becomes densely packed within living cells."
"A Framework for Understanding Biomolecular Condensation"
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"Looking inside chromatin condensates"
"These chromatin condensates, made up of hundreds of thousands of rapidly moving molecules, have emergent properties—behaviors that aren't present in the individual molecules but appear only when they work together as one. These properties dictate how the droplets form and maintain their physical characteristics.
To better understand these qualities, which could help researchers learn how chromatin compacts inside cells, scientists need to peer deep inside the droplets to examine individual chromatin fibers and nucleosomes.
Now, Rosen and his team, along with researchers led by HHMI Investigator Elizabeth Villa at the University of California, San Diego; Rosana Collepardo-Guevara at the University of Cambridge; and Zhiheng Yu at HHMI's Janelia Research Campus; have figured out how to do just that." (video)
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