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HIRA, a mammalian homologue of Saccharomyces cerevisiae transcriptional co-repressors, interacts with Pax3

Nature Genetics volume 20, pages 74–77 (1998)Cite this article

Abstract

HIRA maps to the DiGeorge/velocardiofacial syndrome critical region (DGCR) at 22q11 (Refs 1,2) and encodes a WD40 repeat protein similar to yeast Hir1p and Hir2p. These transcriptional co-repressors regulate cell cycle-dependent histone gene transcription3, possibly by remodelling local chromatin structure. We report an interaction between HIRA and the transcription factor Pax3. Pax3 haploinsufficiency results in the mouse splotch and human Waardenburg syndrome (WSI and WSIII) phenotypes. Mice homozygous for Pax3 mutations die in utero with a phenocopy of DGS, or neonatally with neural tube defects. HIRA was also found to interact with core histones. Thus, altered stoichiometry of complexes containing HIRA may be important for the development of structures affected in WS and DGS.

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Figure 1: HIRA interacts with Pax3, Pax7 and histone H3F3B in vitro.
Figure 2: Mapping the Pax3-binding domain within HIRA.
Figure 3: Co-immunoprecipitation of Pax3 and HIRA from 293 transfected cells.
Figure 4: Co-immunoprecipitation of Pax3 and Hira from whole mouse embryos.
Figure 5: Hira and Pax3 are expressed in neural crest explants.

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Acknowledgements

We would like to thank A. Copp and D. Henderson for Pax3 antibodies, the Pax3-pClneo construct and their generous help. S. Hollenberg supplied two-hybrid reagents, protocols and advice. C. Meijers kindly provided anti-Hira antibody. This work was supported by the British Heart Foundation, the Birth Defects Foundation and MRC (UK), the Ligue Nationale contre le Cancer, AFM, ARC (France) and NATO and the Human Frontier Science Program (UK and France).

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  1. Molecular Medicine Unit, Institute of Child Health , 30 Guilford St., London, WC1N 1EH , U.K.

    Paola Magnaghi, Catherine Roberts & Peter J. Scambler

  2. Laboratoire de Biologie des Tumeurs Humaines, CNRS UMR1598, Institut Gustave-Roussy, Rue Camille Desmoulins, Villejuif Cedex, 94805, France

    Stéphanie Lorain & Marc Lipinski

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Correspondence to Peter J. Scambler.

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Magnaghi, P., Roberts, C., Lorain, S. et al. HIRA, a mammalian homologue of Saccharomyces cerevisiae transcriptional co-repressors, interacts with Pax3. Nat Genet 20, 74–77 (1998). https://doi.org/10.1038/1739

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