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Epigenetic regulation of the interfe...

Kim, Sean Tongwook.

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Epigenetic regulation of the interferon-gamma and interleukin 4 loci in T helper differentiation.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Epigenetic regulation of the interferon-gamma and interleukin 4 loci in T helper differentiation./
作者:	Kim, Sean Tongwook.
面頁冊數:	225 p.
附註:	Source: Dissertation Abstracts International, Volume: 67-04, Section: B, page: 1904.
Contained By:	Dissertation Abstracts International67-04B.
標題:	Biology, Molecular. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3214231
ISBN:	9780542652097

Epigenetic regulation of the interferon-gamma and interleukin 4 loci in T helper differentiation.
Kim, Sean Tongwook.

Epigenetic regulation of the interferon-gamma and interleukin 4 loci in T helper differentiation. - 225 p.

Source: Dissertation Abstracts International, Volume: 67-04, Section: B, page: 1904.

Thesis (Ph.D.)--Yale University, 2006.

T helper differentiation is the process by which CD4+ T lymphocytes develop into IFNgamma-producing Th1 cells, IL4/IL13/IL5-producing Th2 cells, or the newly identified Th17 subset. Because the signature cytokine profile of each subset both shapes and defines lineage commitment, it is of paramount interest to determine how these cytokines are regulated. Here, we present findings demonstrating the epigenetic regulation of T helper development. Firstly, we find that histone H3 and H4 hyperacetylation at the ifn gamma and il4 loci accompany Th1 and Th2 differentiation, respectively. Further, we identify a locus control region (LCR) in the Th2 cytokine cluster based on three epigenetic criteria: DNase I hypersensitivity, histone hyperacetylation, and DNA demethylation. These changes are concurrent with such chromatin remodeling at the il4 locus, suggesting a functional role for the Th2 LCR in coordinating and directing long-range epigenetic changes. Mechanistically, a specific hypersensitive site in the Th2 LCR, RHS7, appears to undergo active, cell division-independent demethylation that is STATE-, IL2-, and CD28-dependent. Finally, we find that biased, proliferation-independent IFNgamma production by gammadelta T cells correlates with a constitutively accessible ifngamma locus, as evidenced by basal level hypomethylation of the first intron. Furthermore, we determine that Eomesodermin and T-bet both have functional roles in gammadelta T cell IFNgamma transactivation. Taken together, these findings demonstrate a strong, lineage-specific epigenetic basis for T helper differentiation in CD4+ and gammadelta T cells.

ISBN: 9780542652097Subjects--Topical Terms:

1017719
Biology, Molecular.

Epigenetic regulation of the interferon-gamma and interleukin 4 loci in T helper differentiation.
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520 $a T helper differentiation is the process by which CD4+ T lymphocytes develop into IFNgamma-producing Th1 cells, IL4/IL13/IL5-producing Th2 cells, or the newly identified Th17 subset. Because the signature cytokine profile of each subset both shapes and defines lineage commitment, it is of paramount interest to determine how these cytokines are regulated. Here, we present findings demonstrating the epigenetic regulation of T helper development. Firstly, we find that histone H3 and H4 hyperacetylation at the ifn gamma and il4 loci accompany Th1 and Th2 differentiation, respectively. Further, we identify a locus control region (LCR) in the Th2 cytokine cluster based on three epigenetic criteria: DNase I hypersensitivity, histone hyperacetylation, and DNA demethylation. These changes are concurrent with such chromatin remodeling at the il4 locus, suggesting a functional role for the Th2 LCR in coordinating and directing long-range epigenetic changes. Mechanistically, a specific hypersensitive site in the Th2 LCR, RHS7, appears to undergo active, cell division-independent demethylation that is STATE-, IL2-, and CD28-dependent. Finally, we find that biased, proliferation-independent IFNgamma production by gammadelta T cells correlates with a constitutively accessible ifngamma locus, as evidenced by basal level hypomethylation of the first intron. Furthermore, we determine that Eomesodermin and T-bet both have functional roles in gammadelta T cell IFNgamma transactivation. Taken together, these findings demonstrate a strong, lineage-specific epigenetic basis for T helper differentiation in CD4+ and gammadelta T cells.
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