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4dn:phase2:interest_groups:phase_separation

Phase Separation

Topic Statement

The nucleus is a crowded mixture of macromolecules that can attain concentrations up to 400 mg/ml, with chromatin comprising a dominant component. Despite such crowding, the nucleus functions like a bustling city with unique and dynamic neighborhoods carrying out distinct sophisticated activities. Phase-separation, a long-observed property of macromolecules at high concentrations, is rapidly emerging as a paradigm to explain intra-nuclear organization. For example, phase-separation may help explain why heterochromatin occupies distinct territories than euchromatin and how transient activation of genes can be enabled through the rapid formation and dissolution of phases containing enhancer-promoter pairs. Yet, we are far from understanding whether and how phase-separation mechanisms in gene regulation exert physiologically relevant effects. Several factors contribute to this conceptual gap: phase-separation behaviors are largely driven by relatively weak, multivalent interactions, which are frequently mediated by disordered protein regions, and we have only just started to uncover the mechanisms and specificity of such interactions. Biological phase-separated condensates, not surprisingly, have complicated compositions involving both protein and nucleic acids. Further, these condensates are heterogeneous in size and shape and can be highly dynamic. This interest group will discuss new findings on the mechanisms and types of condensates and their functional roles in organizing the nucleus.

4dn/phase2/interest_groups/phase_separation.txt · Last modified: 2025/04/22 16:21 (external edit)