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THE MECHANISM OF RECRUITMENT OF TIP60 TO ER TARGET GENES
by
Janet M. Lee
A Thesis Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(BIOCHEMISTRY AND MOLECULAR BIOLOGY)
May 2011
Copyright 2011 Janet M. Lee
Object Description
| Title | The mechanism of recruitment of Tip60 to ER target genes |
| Author | Lee, Janet M. |
| Author email | capricorn134@gmail.com; janetmle@usc.edu |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Biochemistry & Molecular Biology |
| School | Keck School of Medicine |
| Date defended/completed | 2011-02-14 |
| Date submitted | 2011 |
| Restricted until | Unrestricted |
| Date published | 2011-03-07 |
| Advisor (committee member) |
Stallcup, Michael R. Tokes, Zoltan A. Rice, Judd |
| Abstract | The steroid receptors in the nuclear receptor superfamily are responsible for regulating many different functions including transcription. However, in order to completely and correctly activate transcription, the steroid receptors must recruit not only the general initiation factors but also other coregulatory factors, such chromatin remodelers and coactivators. Tip60, a 60 kD protein with an N-terminal chromodomain, a central intrinsic histone acetyltransferase (HAT) activity, and a C-terminal nuclear receptor binding domain (NR box) was previously reported to be a coactivator for androgen receptor, in addition to being able to bind to the estrogen receptor in vivo. Subsequently, Tip60 was identified to be recruited very early on to the pS2 estrogen response element1 (ERE1) site, hormone binding enhancer elements involved in transactivation, upon hormone treatment. Here, it is shown that the interaction between Tip60 and the estrogen receptor, both in vivo and in vitro, requires ligand binding to estrogen receptor and also interacts via the C-terminal NR box, specifically the LXXLL motif. Furthermore, the abolishment of the LXXLL motif compromises Tip60’s recruitment to certain estrogen response elements (EREs) of ER target genes. In addition, the N-terminal chromodomain is shown to preferentially bind to histone H3 mono-methylated and di-methylated at lysine4. Finally, it is shown that a competition for methylated histones between the wildtype Tip60 and the exogenously expressed Tip60 chromodomain fragment also compromises its recruitment to certain EREs of ER target genes. Thus, the stable recruitment and association of Tip60 at the EREs is dependent upon the normal function of its N-terminal chromodomain and C-terminal NR box. |
| Keyword | Tip60; coactivator; nuclear receptor |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m3685 |
| Rights | Lee, Janet M. |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Lee-4369 |
| Archival file | uscthesesreloadpub_Volume48/etd-Lee-4369.pdf |
Description
| Title | Page 1 |
| Full text | THE MECHANISM OF RECRUITMENT OF TIP60 TO ER TARGET GENES by Janet M. Lee A Thesis Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (BIOCHEMISTRY AND MOLECULAR BIOLOGY) May 2011 Copyright 2011 Janet M. Lee |
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