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Regulation of cytokine gene expressi...

Agarwal, Suneet.

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Regulation of cytokine gene expression during T cell differentiation.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Regulation of cytokine gene expression during T cell differentiation./
Author:	Agarwal, Suneet.
Description:	216 p.
Notes:	Source: Dissertation Abstracts International, Volume: 62-04, Section: B, page: 1794.
Contained By:	Dissertation Abstracts International62-04B.
Subject:	Health Sciences, Immunology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3011304
ISBN:	9780493210452

Regulation of cytokine gene expression during T cell differentiation.
Agarwal, Suneet.

Regulation of cytokine gene expression during T cell differentiation. - 216 p.

Source: Dissertation Abstracts International, Volume: 62-04, Section: B, page: 1794.

Thesis (Ph.D.)--Harvard University, 2001.

This thesis examines the regulation of cytokine gene expression, with an emphasis on the role of chromatin structure, during the differentiation of peripheral CD4+ helper T lymphocytes. Helper T lymphocytes undergo two distinct phases of differentiation, resulting in the development of effector T cell subsets displaying mutually exclusive patterns of cytokine gene expression. T helper type-1 (Th1) cells characteristically transcribe the IFN-gamma gene, whereas Th2 cells transcribe the IL-4, IL-5, and IL-13 genes.

ISBN: 9780493210452Subjects--Topical Terms:

1017716
Health Sciences, Immunology.

Regulation of cytokine gene expression during T cell differentiation.
LDR:03397nmm 2200301 4500 001 1820339
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008 130610s2001 eng d
020 $a 9780493210452
035 $a (UnM)AAI3011304
035 $a AAI3011304
040 $a UnM $c UnM
100 1 $a Agarwal, Suneet. $3 1909569
245 1 0 $a Regulation of cytokine gene expression during T cell differentiation.
300 $a 216 p.
500 $a Source: Dissertation Abstracts International, Volume: 62-04, Section: B, page: 1794.
500 $a Adviser: Anjana Rao.
502 $a Thesis (Ph.D.)--Harvard University, 2001.
520 $a This thesis examines the regulation of cytokine gene expression, with an emphasis on the role of chromatin structure, during the differentiation of peripheral CD4+ helper T lymphocytes. Helper T lymphocytes undergo two distinct phases of differentiation, resulting in the development of effector T cell subsets displaying mutually exclusive patterns of cytokine gene expression. T helper type-1 (Th1) cells characteristically transcribe the IFN-gamma gene, whereas Th2 cells transcribe the IL-4, IL-5, and IL-13 genes.
520 $a The transcriptional activity of genetic loci is regulated by structural changes in chromatin, which activate or silence gene transcription. By deoxyribonuclease (DNAse) I hypersensitivity analysis of the endogenous murine IL-4, IL-13 and IFN-gamma loci, we found that the initial response of naive T cells to antigen was accompanied by long-range changes in the chromatin structure of effector cytokine genes. Differentiation of naive T cells into effector Th2 cells was associated with chromatin remodeling throughout a 43 kb interval spanning the linked IL-4/IL-13 loci, suggesting coordinate regulation of these genes at the level of chromatin. In contrast, differentiation of the same precursor population into Th1 cells evoked chromatin remodeling of the IFN-gamma but not of the IL-4/IL-13 locus. IL-4 locus remodeling was accompanied by demethylation and required both antigen stimulation and STAT6 activation. Antigenic stimulation of Th2 cells resulted in the induction of a novel DNAse I hypersensitive site in the IL-4 locus, which contained transcriptional enhancer activity in vivo. The enhancer contained consensus binding sites for the antigen-induced transcription factor NFAT, which was bound to the endogenous enhancer only in stimulated Th2 cells.
520 $a Together, our results support a model whereby signaling pathways initiated in naive T cells by primary contact with antigen and cytokines recruit nuclear factors and chromatin remodeling enzymes to novel regulatory regions in cytokine genetic loci. Upon subsequent antigenic stimulation, transcription factors such as NFAT gain access to cytokine regulatory regions only in the appropriate subset of differentiated T cells in vivo, enabling antigen-dependent and subset-specific transcription of cytokine genes. Further analysis of mice carrying targeted deletions of DNAse I hypersensitive sites will permit a functional analysis of these potential regulatory elements in the endogenous cytokine genetic loci.
590 $a School code: 0084.
650 4 $a Health Sciences, Immunology. $3 1017716
650 4 $a Biology, Molecular. $3 1017719
690 $a 0982
690 $a 0307
710 2 0 $a Harvard University. $3 528741
773 0 $t Dissertation Abstracts International $g 62-04B.
790 1 0 $a Rao, Anjana, $e advisor
790 $a 0084
791 $a Ph.D.
792 $a 2001
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3011304