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The role of the glucocorticoid recep...

Keeton, Erika Krasnickas.

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The role of the glucocorticoid receptor domains in remodeling chromatin and activating transcription in different nucleoprotein contexts using the MMTV promoter as a model system.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	The role of the glucocorticoid receptor domains in remodeling chromatin and activating transcription in different nucleoprotein contexts using the MMTV promoter as a model system./
作者:	Keeton, Erika Krasnickas.
面頁冊數:	159 p.
附註:	Directors: Catharine L. Smith; Gordon L. Hager.
Contained By:	Dissertation Abstracts International62-11B.
標題:	Biology, Genetics. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3032752
ISBN:	0493452494

The role of the glucocorticoid receptor domains in remodeling chromatin and activating transcription in different nucleoprotein contexts using the MMTV promoter as a model system.
Keeton, Erika Krasnickas.

The role of the glucocorticoid receptor domains in remodeling chromatin and activating transcription in different nucleoprotein contexts using the MMTV promoter as a model system. - 159 p.

Directors: Catharine L. Smith; Gordon L. Hager.

Thesis (Ph.D.)--The George Washington University, 2002.

The glucocorticoid receptor (GR) functions as a ligand-activated transcription factor to mediate the biological effects of glucocorticoids. To activate transcription, the GR binds to glucocorticoid response elements (GREs) in the regulatory regions of target genes, which are packaged into chromatin. The mouse mammary tumor virus (MMTV) promoter is an excellent model to study the mechanism of transcriptional activation by the GR in the context of chromatin. The promoter adopts distinct chromatin structures when it is stably replicating versus transiently transfected, leading to different mechanisms of activation by the GR. The stably replicating promoter adopts an ordered chromatin structure, leading to a bimodal mechanism of activation that involves derepression (chromatin remodeling) and subsequent activation. The transient template adopts a disorganized chromatin structure and only requires an activation step. We wanted to gain a better understanding of the requirements for activation in the two chromatin contexts.

ISBN: 0493452494Subjects--Topical Terms:

1017730
Biology, Genetics.

The role of the glucocorticoid receptor domains in remodeling chromatin and activating transcription in different nucleoprotein contexts using the MMTV promoter as a model system.
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245 1 0 $a The role of the glucocorticoid receptor domains in remodeling chromatin and activating transcription in different nucleoprotein contexts using the MMTV promoter as a model system.
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500 $a Directors: Catharine L. Smith; Gordon L. Hager.
500 $a Source: Dissertation Abstracts International, Volume: 62-11, Section: B, page: 4916.
502 $a Thesis (Ph.D.)--The George Washington University, 2002.
520 $a The glucocorticoid receptor (GR) functions as a ligand-activated transcription factor to mediate the biological effects of glucocorticoids. To activate transcription, the GR binds to glucocorticoid response elements (GREs) in the regulatory regions of target genes, which are packaged into chromatin. The mouse mammary tumor virus (MMTV) promoter is an excellent model to study the mechanism of transcriptional activation by the GR in the context of chromatin. The promoter adopts distinct chromatin structures when it is stably replicating versus transiently transfected, leading to different mechanisms of activation by the GR. The stably replicating promoter adopts an ordered chromatin structure, leading to a bimodal mechanism of activation that involves derepression (chromatin remodeling) and subsequent activation. The transient template adopts a disorganized chromatin structure and only requires an activation step. We wanted to gain a better understanding of the requirements for activation in the two chromatin contexts.
520 $a Transcriptional activation by the GR can be mediated by at least three domains, τ1 (AF1), τ2 and AF2, which were defined using transiently transfected target templates. The τ1 and AF2 domains have been shown to interact with several coactivators, some of which possess histone acetyltransferase or nucleosome remodeling activity and may thereby remodel chromatin structure. Using receptors with mutations in these domains, we determined their relative importance in activating transient and stable MMTV templates. We found differences in the contribution of the domains to activation of the two templates. The AF2 domain was important for activation of the transient template, whereas the τ1 domain was not. On the stable template, the AF2 domain appeared to play an indirect role in chromatin remodeling, whereas the τ1 domain was required downstream for activation. Receptors with both domains mutated were able to fully remodel chromatin leading to the identification of additional receptor domains involved in chromatin remodeling. These findings indicate that the GR can use different domains, and potentially distinct coactivators, to activate transcription on the two templates and that nucleoprotein structure can determine the mechanism of activation. These results also provide new insight into how the domains function to activate transcription in a complex chromatin environment.
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