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

Hummel, Barbara; Hansen, Erik C.; Yoveva, Aneliya; Aprile-Garcia, Fernando; Hussong, Rebecca; Sawarkar, Ritwick

doi:10.1038/nsmb.3368

Item

ITEM ACTIONSEXPORT

Add to Basket

Please note that a newer version of this item is available:
https://pure.mpg.de/pubman/item/item_2457170_3

DetailsSummary

Released

Journal Article

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

MPS-Authors

Hummel, Barbara
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Hansen, Erik C.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Yoveva, Aneliya
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;
Faculty of Biology, University of Freiburg;

Aprile-Garcia, Fernando
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Hussong, Rebecca
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Sawarkar, Ritwick
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

External Resource

No external resources are shared

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

There is no public supplementary material available

Citation

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.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002E-85ED-4

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.