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Comprehensive epigenetic profiling i...

Schoenborn, Jamie R.

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Comprehensive epigenetic profiling identifies multiple distal regulatory elements directing lfng transcription.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Comprehensive epigenetic profiling identifies multiple distal regulatory elements directing lfng transcription./
作者:	Schoenborn, Jamie R.
面頁冊數:	144 p.
附註:	Adviser: Christopher B. Wilson.
Contained By:	Dissertation Abstracts International68-05B.
標題:	Biology, Molecular. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3265406
ISBN:	9780549039334

Comprehensive epigenetic profiling identifies multiple distal regulatory elements directing lfng transcription.
Schoenborn, Jamie R.

Comprehensive epigenetic profiling identifies multiple distal regulatory elements directing lfng transcription. - 144 p.

Adviser: Christopher B. Wilson.

Thesis (Ph.D.)--University of Washington, 2007.

Interferon-gamma (IFN-gamma) is critical for innate and adaptive immunity against viral and intracellular bacterial infections. In humans, genetic defects resulting in impaired IFN-gamma secretion or signaling are associated with increased susceptibility to mycobacterial and Salmonella infection. Furthermore, IFN-gamma is involved in tumor control, whereby it enhances the immunogenicity of tumor cells and stimulates the immune response to transformed cells. Produced by NK cells during innate immunity and by CD8 and CD4 Th1 cells of the adaptive immune system, IFN-gamma directly blocks viral replication, increases antigen presentation, primes macrophages to produce potent antimicrobial products and is an immunostimulatory molecule that activates CD4 Th1 differentiation. Whereas much known about the cellular signals and the activation of downstream signaling pathways and transcription factors that contribute to IFN-gamma secretion, very little is known about cis-regulatory elements within the Ifng gene itself. I have used a combination of computational, chromatin-based and functional approaches to survey the genome surrounding Ifng to identify distal regulatory elements that help govern the expression of this gene. Comparative genomic analysis revealed gene(s) belonging to the IL-10 family and a housekeeping gene, Mdm1, as the nearest neighbors of Ifng. The murine Ifng locus diverges from the ancestral locus 57 kb upstream of Ifng due to structural rearrangements by repetitive elements. Within a syntenic 120 kb region surrounding the Ifng gene are eight highly conserved non-coding regions (CNSs) that are enriched in distinct CD4 T cell subset-specific epigenetic and chromatin modifications. Some CNSs were found to enhance IFN-gamma expression in response to signals downstream of the TCR or NK activating receptors, or IL-12 plus IL-18 cytokine receptors, or in response to T-bet. Furthermore, some CNSs acted as insulators or enhancer-blocking elements to protect Ifng from the effects of neighboring chromatin and regulatory elements. Together, these data define the structure of the Ifng locus and identify regions that are likely to play major roles in the regulation of its expression through the binding of transcription factors and other protein mediators that subsequently are responsible for the potentiation of gene expression or silencing of the locus in non-expressing cell types.

ISBN: 9780549039334Subjects--Topical Terms:

1017719
Biology, Molecular.

Comprehensive epigenetic profiling identifies multiple distal regulatory elements directing lfng transcription.
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