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Molecular and Cellular Biology, September 1998, p. 5546-5556, Vol. 18, No. 9
Biologie des Tumeurs Humaines,
Received 23 January 1998/Returned for modification 5 March
1998/Accepted 10 June 1998
The human HIRA gene has been named after Hir1p and
Hir2p, two corepressors which together appear to act on chromatin
structure to control gene transcription in Saccharomyces
cerevisiae. HIRA homologs are expressed in a regulated fashion
during mouse and chicken embryogenesis, and the human gene is a major
candidate for the DiGeorge syndrome and related developmental disorders caused by a reduction to single dose of a fragment of chromosome 22q.
Western blot analysis and double-immunofluorescence experiments using a
specific antiserum revealed a primary nuclear localization of
HIRA. Similar to Hir1p, HIRA contains seven amino-terminal WD
repeats and probably functions as part of a multiprotein complex. HIRA
and core histone H2B were found to physically interact in a yeast
double-hybrid protein interaction trap, in GST pull-down assays, and in
coimmunoprecipitation experiments performed from cellular extracts. In
vitro, HIRA also interacted with core histone H4. H2B- and H4-binding
domains were overlapping but distinguishable in the carboxy-terminal
region of HIRA, and the region for HIRA interaction was mapped to the
amino-terminal tail of H2B and the second
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Core Histones and HIRIP3, a Novel Histone-Binding
Protein, Directly Interact with WD Repeat Protein HIRA
helix of H4. HIRIP3
(HIRA-interacting protein 3) is a novel gene product that was
identified from its HIRA-binding properties in the yeast protein
interaction trap. In vitro, HIRIP3 directly interacted with HIRA but
also with core histones H2B and H3, suggesting that a
HIRA-HIRIP3-containing complex could function in some aspects of
chromatin and histone metabolism. Insufficient production of HIRA,
which we report elsewhere interacts with homeodomain-containing DNA-binding factors during mammalian embryogenesis, could perturb the
stoichiometric assembly of multimolecular complexes required for normal
embryonic development.
*
Corresponding author. Mailing address: Laboratoire de
Biologie des Tumeurs Humaines, CNRS UMR 1598, Rue Camille Desmoulins, Institut Gustave Roussy, 94805 Villejuif Cedex, France. Phone: 33 1 42 11 49 17. Fax: 33 1 42 11 54 94. E-mail: lipinski{at}igr.fr.
Molecular and Cellular Biology, September 1998, p. 5546-5556, Vol. 18, No. 9
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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