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Open Access Highly Accessed Research article

Drosophila GAGA factor polyglutamine domains exhibit prion-like behavior

Muhammad Tariq1*, Renee Wegrzyn4, Saima Anwar1, Bernd Bukau4 and Renato Paro23

Author Affiliations

1 Department of Biology, SBA School of Science and Engineering, Lahore University of Management Sciences, Lahore 54792, Pakistan

2 Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, Basel 4058, Switzerland

3 Faculty of Science, University of Basel, Basel 4056, Switzerland

4 Zentrum für Molekulare Biologie Heidelberg, Im Neuenheimer Feld 282, Heidelberg 69120, Germany

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BMC Genomics 2013, 14:374  doi:10.1186/1471-2164-14-374

Published: 3 June 2013

Abstract

Background

The Drosophila GAGA factor (GAF) participates in nucleosome remodeling to activate genes, acts as an antirepressor and is associated with heterochromatin, contributing to gene repression. GAF functions are intimately associated to chromatin-based epigenetic control, linking basic transcriptional regulation to heritable long-term maintenance of gene expression. These diverse functions require GAF to interact with different partners in different multiprotein complexes. The two isoforms of GAF depict highly conserved glutamine-rich C-terminal domains (Q domain), which have been implicated in complex formation.

Results

Here we show that the Q domains exhibit prion-like properties. In an established yeast test system the two GAF Q domains convey prion activities comparable to well known yeast prions. The Q domains stably maintain two distinct conformational states imposing functional constraints on the fused yeast reporter protein. The prion-like phenotype can be reversibly cured in the presence of guanidine HCl or by over-expression of the Hsp104 chaperone protein. Additionally, when fused to GFP, the Q domains form aggregates in yeast cells.

Conclusion

We conclude that prion-like behavior of the GAF Q domain suggests that this C-terminal structure may perform stable conformational switches. Such a self-perpetuating change in the conformation could assist GAF executing its diverse epigenetic functions of gene control in Drosophila.

Keywords:
GAGA factor; Epigenetics; Prion-like; Chromatin