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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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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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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DOI: https://doi.org/10.1038/1739
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