Long-distance association of topological boundaries through nuclear condensates.

Autor: Gamliel A; Department of Medicine, University of California San Diego, La Jolla, CA 92093.; HHMI, University of California San Diego, La Jolla, CA 92093., Meluzzi D; Department of Medicine, University of California San Diego, La Jolla, CA 92093.; HHMI, University of California San Diego, La Jolla, CA 92093., Oh S; Department of Medicine, University of California San Diego, La Jolla, CA 92093.; HHMI, University of California San Diego, La Jolla, CA 92093., Jiang N; Department of Neurosciences, University of California San Diego, La Jolla, CA 92093., Destici E; Department of Neurosciences, University of California San Diego, La Jolla, CA 92093., Rosenfeld MG; Department of Medicine, University of California San Diego, La Jolla, CA 92093.; HHMI, University of California San Diego, La Jolla, CA 92093., Nair SJ; Department of Medicine, University of California San Diego, La Jolla, CA 92093.; HHMI, University of California San Diego, La Jolla, CA 92093.
Jazyk: angličtina
Zdroj: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2022 Aug 09; Vol. 119 (32), pp. e2206216119. Date of Electronic Publication: 2022 Aug 01.
DOI: 10.1073/pnas.2206216119
Abstrakt: The eukaryotic genome is partitioned into distinct topological domains separated by boundary elements. Emerging data support the concept that several well-established nuclear compartments are ribonucleoprotein condensates assembled through the physical process of phase separation. Here, based on our demonstration that chemical disruption of nuclear condensate assembly weakens the insulation properties of a specific subset (∼20%) of topologically associated domain (TAD) boundaries, we report that the disrupted boundaries are characterized by a high level of transcription and striking spatial clustering. These topological boundary regions tend to be spatially associated, even interchromosomally, segregate with nuclear speckles, and harbor a specific subset of "housekeeping" genes widely expressed in diverse cell types. These observations reveal a previously unappreciated mode of genome organization mediated by conserved boundary elements harboring highly and widely expressed transcription units and associated transcriptional condensates.
Databáze: MEDLINE