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Spatiotemporal regulation of liquid-like condensates in epigenetic inheritance.

Authors
  • Wan, Gang1
  • Fields, Brandon D1, 2
  • Spracklin, George1, 2
  • Shukla, Aditi1
  • Phillips, Carolyn M3
  • Kennedy, Scott4
  • 1 Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • 2 Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI, USA.
  • 3 Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA.
  • 4 Department of Genetics, Harvard Medical School, Boston, MA, USA. [email protected]
Type
Published Article
Journal
Nature
Publisher
Springer Nature
Publication Date
May 01, 2018
Volume
557
Issue
7707
Pages
679–683
Identifiers
DOI: 10.1038/s41586-018-0132-0
PMID: 29769721
Source
Medline
License
Unknown

Abstract

Non-membrane-bound organelles such as nucleoli, processing bodies, Cajal bodies and germ granules form by the spontaneous self-assembly of specific proteins and RNAs. How these biomolecular condensates form and interact is poorly understood. Here we identify two proteins, ZNFX-1 and WAGO-4, that localize to Caenorhabditis elegans germ granules (P granules) in early germline blastomeres. Later in germline development, ZNFX-1 and WAGO-4 separate from P granules to define an independent liquid-like condensate that we term the Z granule. In adult germ cells, Z granules assemble into ordered tri-condensate assemblages with P granules and Mutator foci, which we term PZM granules. Finally, we show that one biological function of ZNFX-1 and WAGO-4 is to interact with silencing RNAs in the C. elegans germline to direct transgenerational epigenetic inheritance. We speculate that the temporal and spatial ordering of liquid droplet organelles may help cells to organize and coordinate the complex RNA processing pathways that underlie gene-regulatory systems, such as RNA-directed transgenerational epigenetic inheritance.

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