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  The evolutionary capacitor HSP90 buffers the regulatory effects of mammalian endogenous retroviruses

Hummel, B., Hansen, E. C., Yoveva, A., Aprile-Garcia, F., Hussong, R., & Sawarkar, R. (2017). The evolutionary capacitor HSP90 buffers the regulatory effects of mammalian endogenous retroviruses. Nature Structural and Molecular Biology, 234-242. doi:10.1038/nsmb.3368.

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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-002E-85ED-4 Version Permalink: https://hdl.handle.net/11858/00-001M-0000-002E-85EE-2
Genre: Journal Article

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 Creators:
Hummel, Barbara1, Author
Hansen, Erik C.1, Author
Yoveva, Aneliya1, 2, Author
Aprile-Garcia, Fernando1, Author
Hussong, Rebecca1, Author
Sawarkar, Ritwick1, Author
Affiliations:
1Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              
2Faculty of Biology, University of Freiburg, Freiburg, Germany, ou_persistent22              

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 Abstract: Understanding how genotypes are linked to phenotypes is important in biomedical and evolutionary studies. The chaperone heat-shock protein 90 (HSP90) buffers genetic variation by stabilizing proteins with variant sequences, thereby uncoupling phenotypes from genotypes. Here we report an unexpected role of HSP90 in buffering cis-regulatory variation affecting gene expression. By using the tripartite-motif-containing 28 (TRIM28; also known as KAP1)-mediated epigenetic pathway, HSP90 represses the regulatory influence of endogenous retroviruses (ERVs) on neighboring genes that are critical for mouse development. Our data based on natural variations in the mouse genome show that genes respond to HSP90 inhibition in a manner dependent on their genomic location with regard to strain-specific ERV-insertion sites. The evolutionary-capacitor function of HSP90 may thus have facilitated the exaptation of ERVs as key modifiers of gene expression and morphological diversification. Our findings add a new regulatory layer through which HSP90 uncouples phenotypic outcomes from individual genotypes.

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Language(s): eng - English
 Dates: 2017-03
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1038/nsmb.3368
 Degree: -

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Title: Nature Structural and Molecular Biology
  Other : Nature Struct Biol
Source Genre: Journal
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Publ. Info: New York, NY : Nature Pub. Group
Pages: - Volume / Issue: - Sequence Number: - Start / End Page: 234 - 242 Identifier: ISSN: 1545-9993
CoNE: https://pure.mpg.de/cone/journals/resource/954925603763