Remodelling of the S3 PA700 proteasome activator gene chromatin structure during thymocyte differentiation
Remodelling of the S3 PA700 proteasome activator gene chromatin structure during thymocyte differentiation
The proteasome is the major cytosolic protease, composed of a 20S catalytic core that associates with either the 19S (PA700) activator or the 11S (PA28) regulator complex. The 19S complex is thought to promote protein substrate unfolding and subsequent degradation, but precise functions for the individual subunits remain undefined. The chromatin structure and regulation of the S3 (P91A) subunit of the 19S activator was examined as a novel approach towards understanding its role in the complex. DNase I hypersensitivity (HS) analysis of S3 chromatin revealed a ubiquitous DNase I HS site mapping to the promoter region. Examination of the S3 chromatin structure in thymocytes, a dynamic population that undergo substantial proliferation, apoptosis, and differentiation, revealed an additional DNase I HS site mapping to the sixth intron of the genomic sequence. This second site was demonstrated to be associated with CD4+CD8+ double-positive (DP) but not CD4+ single-positive (SP) thymoma cell lines, and may correlate with a downregulation of S3 message. When a DP thymic cell line was induced to differentiate through retroviral transduction with Notch-1, the second DNase I HS site was dramatically diminished, illustrating that S3 chromatin is developmentally regulated during thymocyte positive selection.
S3, P91A, proteasome, thymocyte, differentiation
260-267
Antoniou, Antony N.
3d711a3b-f688-46f9-823e-5bb925d10ea8
Moore, Nel
d9df341b-41e0-4e0a-8f5c-9f07df50ebd4
Dyson, Julian P.
355cb8a3-df2a-4a4c-978a-1078be5a5f99
2002
Antoniou, Antony N.
3d711a3b-f688-46f9-823e-5bb925d10ea8
Moore, Nel
d9df341b-41e0-4e0a-8f5c-9f07df50ebd4
Dyson, Julian P.
355cb8a3-df2a-4a4c-978a-1078be5a5f99
Antoniou, Antony N., Moore, Nel and Dyson, Julian P.
(2002)
Remodelling of the S3 PA700 proteasome activator gene chromatin structure during thymocyte differentiation.
Immunogenetics, 54 (4), .
(doi:10.1007/s00251-002-0475-3).
Abstract
The proteasome is the major cytosolic protease, composed of a 20S catalytic core that associates with either the 19S (PA700) activator or the 11S (PA28) regulator complex. The 19S complex is thought to promote protein substrate unfolding and subsequent degradation, but precise functions for the individual subunits remain undefined. The chromatin structure and regulation of the S3 (P91A) subunit of the 19S activator was examined as a novel approach towards understanding its role in the complex. DNase I hypersensitivity (HS) analysis of S3 chromatin revealed a ubiquitous DNase I HS site mapping to the promoter region. Examination of the S3 chromatin structure in thymocytes, a dynamic population that undergo substantial proliferation, apoptosis, and differentiation, revealed an additional DNase I HS site mapping to the sixth intron of the genomic sequence. This second site was demonstrated to be associated with CD4+CD8+ double-positive (DP) but not CD4+ single-positive (SP) thymoma cell lines, and may correlate with a downregulation of S3 message. When a DP thymic cell line was induced to differentiate through retroviral transduction with Notch-1, the second DNase I HS site was dramatically diminished, illustrating that S3 chromatin is developmentally regulated during thymocyte positive selection.
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Published date: 2002
Keywords:
S3, P91A, proteasome, thymocyte, differentiation
Identifiers
Local EPrints ID: 26195
URI: http://eprints.soton.ac.uk/id/eprint/26195
PURE UUID: 7191eb83-8b10-4050-b8a1-970e7989f34e
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Date deposited: 20 Apr 2006
Last modified: 15 Mar 2024 07:08
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Contributors
Author:
Antony N. Antoniou
Author:
Nel Moore
Author:
Julian P. Dyson
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