The hairless gene mutated in congenital hair loss disorders encodes a novel nuclear receptor corepressor

G. B. Potter, G. M.J. Beaudoin, C. L. DeRenzo, J. M. Zarach, S. H. Chen, C. C. Thompson

    Research output: Contribution to journalArticle

    140 Scopus citations

    Abstract

    The mammalian hairless (hr) gene plays a critical role in the maintenance of hair growth. Although the hr gene has been identified, the biochemical function of its encoded protein (Hr) has remained obscure. Here, we show that Hr functions as a transcriptional corepressor for thyroid hormone receptors (TRs). We find that two independent regions of Hr mediate TR binding and that interaction requires a cluster of hydrophobic residues similar to the binding motifs proposed for nuclear receptor corepressors (N-CoR and SMRT). Similarly, we show that Hr binds to the same region of TR as known corepressors. We show that Hr interacts with histone deacetylases (HDACs) and is localized to matrix-associated deacetylase (MAD) bodies, indicating that the mechanism of Hr-mediated repression is likely through associated HDAC activity. Thus, Hr is a component of the corepressor machinery, and despite its lack of sequence identity with previously described corepressors, its mode of action is remarkably conserved. On the basis of its thyroid hormone-inducible and tissue- and developmental-specific expression, Hr likely defines a new class of nuclear receptor corepressors that serve a more specialized role than ubiquitous corepressors. The discovery that Hr is a corepressor provides a molecular basis for specific hair loss syndromes in both humans and mice.

    Original languageEnglish (US)
    Pages (from-to)2687-2701
    Number of pages15
    JournalGenes and Development
    Volume15
    Issue number20
    DOIs
    StatePublished - Oct 15 2001

    Keywords

    • Histone deacetylase
    • Nuclear receptor
    • Thyroid hormone
    • Transcriptional repression

    ASJC Scopus subject areas

    • Genetics
    • Developmental Biology

    Fingerprint Dive into the research topics of 'The hairless gene mutated in congenital hair loss disorders encodes a novel nuclear receptor corepressor'. Together they form a unique fingerprint.

  • Cite this

    Potter, G. B., Beaudoin, G. M. J., DeRenzo, C. L., Zarach, J. M., Chen, S. H., & Thompson, C. C. (2001). The hairless gene mutated in congenital hair loss disorders encodes a novel nuclear receptor corepressor. Genes and Development, 15(20), 2687-2701. https://doi.org/10.1101/gad.916701