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The function of histone acetyltransferase GCN5 in transcription regulation.

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Format:
Book
Thesis/Dissertation
Author/Creator:
Wang, Lian.
Contributor:
Berger, S. L. (Shelley L.), advisor.
University of Pennsylvania.
Language:
English
Subjects (All):
Molecular biology.
0307.
Penn dissertations--Biochemistry.
Biochemistry--Penn dissertations.
Local Subjects:
Penn dissertations--Biochemistry.
Biochemistry--Penn dissertations.
0307.
Physical Description:
144 pages
Contained In:
Dissertation Abstracts International 58-07B.
System Details:
Mode of access: World Wide Web.
text file
Summary:
Transcriptional adaptor proteins are thought to regulate transcriptional activation by facilitating productive interactions between the transcriptional basal machinery and activators. Histone acetyltransferases (HATs) may potentiate transcription by alleviating repressive nucleosome structure. This work has focused on the relationship between transcriptional activation and histone acetylation, as both can be carried out by the adaptor GCN5. First, human homologues of yeast adaptor proteins ADA2 and GCN5 were identified by sequence conservation and isolated by hybridization screening. Though unable to complement in yeast, these human homologues could interact with each other in a way similar to their yeast counterparts. Moreover, these human proteins could potentiate transcriptional activation in HeLa cells, suggesting that they might also function as bridging proteins between transcriptional basal machinery and activators. Upon the discovery that yeast GCN5 possesses HAT activity, it was shown that human GCN5 could also acetylate histones, and the HAT domain of human GCN5 had conserved function for complementation of growth and transcriptional activation in yeast. Finally, a strong correlation between nucleosomal histone acetylation activity and in vivo function, including transcriptional activation, was established by a detailed alanine-scan mutagenesis study in the HAT domain of yeast GCN5, and possible active sites of HAT activity were mapped. Thus, these data support a model for the function of adaptor proteins: histone acetylation is targeted to specific promoters by interaction between adaptor proteins and specific activators, then, basal machinery recruitment is accelerated by both interactions with adaptor proteins and targeted histone acetylation.
Notes:
Thesis (Ph.D. in Biochemistry) -- University of Pennsylvania, 1997.
Source: Dissertation Abstracts International, Volume: 58-07, Section: B, page: 3484.
Supervisor: Shelley L. Berger.
Local Notes:
School code: 0175.
ISBN:
9780591501872
Access Restriction:
Restricted for use by site license.

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