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Regulation of gene expression in T l...

Harvard University.

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Regulation of gene expression in T lymphocytes by the transcription factor Runx3.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Regulation of gene expression in T lymphocytes by the transcription factor Runx3./
作者:	Djuretic, Ivana.
面頁冊數:	200 p.
附註:	Adviser: Anjana Rao.
Contained By:	Dissertation Abstracts International70-03B.
標題:	Biology, Molecular. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3350955
ISBN:	9781109066524

Regulation of gene expression in T lymphocytes by the transcription factor Runx3.
Djuretic, Ivana.

Regulation of gene expression in T lymphocytes by the transcription factor Runx3. - 200 p.

Adviser: Anjana Rao.

Thesis (Ph.D.)--Harvard University, 2009.

T lymphocytes have served as a model system for studying gene regulation and cell fate decisions in many laboratories over the last two decades. In particular, the differentiation of antigen-inexperienced (naive) T helper cells upon encounter of antigen has received the most attention, as this process can be very efficiently and accurately recapitulated in vitro. T helper (TH) differentiation results in the acquisition of specialized effector functions (i.e. secretion of cytokines) that enable T helper cells to direct appropriate and effective immune responses against a great diversity of pathogens. Thus, dramatic changes in transcriptional profiles occur during this process resulting in selective activation and silencing of the transcriptional potential of cytokine genes (e.g. activation of interferon-gamma [IFN-gamma] and silencing of interleukin-4 [IL-4] during T helper-1 differentiation).

ISBN: 9781109066524Subjects--Topical Terms:

1017719
Biology, Molecular.

Regulation of gene expression in T lymphocytes by the transcription factor Runx3.
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245 1 0 $a Regulation of gene expression in T lymphocytes by the transcription factor Runx3.
300 $a 200 p.
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500 $a Source: Dissertation Abstracts International, Volume: 70-03, Section: B, page: 1579.
502 $a Thesis (Ph.D.)--Harvard University, 2009.
520 $a T lymphocytes have served as a model system for studying gene regulation and cell fate decisions in many laboratories over the last two decades. In particular, the differentiation of antigen-inexperienced (naive) T helper cells upon encounter of antigen has received the most attention, as this process can be very efficiently and accurately recapitulated in vitro. T helper (TH) differentiation results in the acquisition of specialized effector functions (i.e. secretion of cytokines) that enable T helper cells to direct appropriate and effective immune responses against a great diversity of pathogens. Thus, dramatic changes in transcriptional profiles occur during this process resulting in selective activation and silencing of the transcriptional potential of cytokine genes (e.g. activation of interferon-gamma [IFN-gamma] and silencing of interleukin-4 [IL-4] during T helper-1 differentiation).
520 $a In an effort to study the mechanism of silencing of one essential T helper cytokine, IL-4, we discovered a role for the Runx family of transcription factors in TH differentiation. We demonstrate that the transcription factor Runx3 is induced after activation of naive TH cells under conditions that promote their differentiation into the TH1 (IFN-gamma-secreting), but not the TH2 (IL-4 secreting) lineage. Runx3 induction was dependent on the transcription factor T-bet, essential regulator of TH1 differentiation, and Runx3 and T-bet cooperated and were both required for TH1-specific gene activation and silencing.
520 $a Furthermore, we focus on the function of Runx3 as a transcriptional repressor, and find that Runx3 mediated silencing of the Il4 gene at the level of chromatin structure. Specifically, Runx3 bound to the Il4 silencer element, HS IV, and recruited the Groucho family of corepressors to the Il4 locus. We show that binding of Runx3 and Groucho to HS IV is required for the induction of a proper pattern of chromatin modifications at the Il4 locus. Taken together, these results provide a more detailed view of the transcriptional networks that regulate T cell differentiation and of the mechanisms that transcription factors use to regulate gene expression in T lymphocytes.
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