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Citation
Tariq, M., Nussbaumer, U., Chen, Y., Beisel, C., Paro, R. (2009). Trithorax requires Hsp90 for maintenance of active chromatin at sites of gene expression.  Proc. Natl. Acad. Sci. U.S.A. 106(4): 1157--1162.
FlyBase ID
FBrf0215368
Publication Type
Research paper
Abstract
Molecular chaperone heat-shock protein 90 kDa (Hsp90) is known to facilitate the conformational maturation of a diverse range of proteins involved in different signal transduction pathways during development. Recent studies have implicated Hsp90 in transcriptional regulation and an important role for Hsp90 in epigenetic processes has been proposed. Importantly, genetic and pharmacological perturbation of Hsp90 was shown to reveal heritable phenotypic variation and Hsp90 was found to play an important role in buffering genetic and epigenetic variation whose expression led to altered phenotypes. The underlying molecular mechanism remains elusive, however. Here, we show a direct molecular interaction between Hsp90 and Trithorax (Trx). Trx is a member of the TrxG chromatin proteins controlling, together with the members of the Polycomb group, the developmental fate of cells by modulating epigenetic signals. Hsp90 cooperates with Trx at chromatin for maintaining the active expression state of targets like the Hox genes. Pharmacological inhibition of Hsp90 results in degradation of Trx and a concomitant down-regulation of homeotic gene expression. A similar effect is observed with the human orthologue mixed-lineage leukemia. Connecting an epigenetic network controlling major developmental and cellular pathways with a system sensing external cues may explain the rapid fixation and epigenetic inheritance of phenotypic variation as a result of impaired Hsp90.
PubMed ID
PubMed Central ID
PMC2633526 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Proc. Natl. Acad. Sci. U.S.A.
    Title
    Proceedings of the National Academy of Sciences of the United States of America
    Publication Year
    1915-
    ISBN/ISSN
    0027-8424
    Data From Reference
    Alleles (8)
    Genes (8)
    Physical Interactions (2)
    Cell Lines (1)
    Natural transposons (1)
    Experimental Tools (1)
    Transgenic Constructs (1)