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Global analyses of STAT target selec...

Hartman, Stephen Edward.

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Global analyses of STAT target selection and transcription regulation.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Global analyses of STAT target selection and transcription regulation./
Author:	Hartman, Stephen Edward.
Description:	151 p.
Notes:	Source: Dissertation Abstracts International, Volume: 67-04, Section: B, page: 1828.
Contained By:	Dissertation Abstracts International67-04B.
Subject:	Biology, Molecular. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3214218
ISBN:	9780542651953

Global analyses of STAT target selection and transcription regulation.
Hartman, Stephen Edward.

Global analyses of STAT target selection and transcription regulation. - 151 p.

Source: Dissertation Abstracts International, Volume: 67-04, Section: B, page: 1828.

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

The interferons (IFNs) are important regulators of vital biological processes such as antiviral defense responses, regulation of cell proliferation, apoptosis, and immune responses. The STAT (s&barbelow;ignal t&barbelow;ransducer and a&barbelow;ctivator of t&barbelow;ranscription) family of proteins mediates the transcriptional responses to many cytokines and growth factors, including the IFNs. Much research has focused on understanding STAT activation, regulation, structure, and the phenotypic effects of their absence. However, significantly less progress has been made toward identifying the specific STAT-regulated genes crucial for mediating the biological effects of the IFNs and determining how these targets are selected. We have addressed this by identifying the binding sites and target genes of IFN-activated STATs using DNA microarrays. At the present time, DNA microarrays are the most suitable technology for the unbiased exploration of gene regulation. We have utilized a combination of different microarray designs, experimental techniques, and analysis strategies to define the DNA binding sites and target genes of STAT1 and STAT2 in humans, as well as the gene transcription events under their control. First, we combined the ChIP-chip and expression profiling microarray approaches to study the activities of IFN-alpha, IFN-gamma, STAT1, and STAT2 along human chromosome 22. These experiments revealed a large amount of previously unrecognized IFN/STAT activity on human chromosome 22, as well as introduced novel mechanisms for the regulation of STAT1 binding site selection. We have also performed full-human genome IFN-induced gene expression profiling experiments using STAT-deficient cell lines. Our results have uncovered a large number of novel IFN-up- and down-regulated genes that depend upon specific STATs for their regulation. Finally, our focused characterization of two of these novel genes led to our discovery of a STAT3-mediated mechanism of inappropriate gene regulation in B-cell lymphoma.

ISBN: 9780542651953Subjects--Topical Terms:

1017719
Biology, Molecular.

Global analyses of STAT target selection and transcription regulation.
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245 1 0 $a Global analyses of STAT target selection and transcription regulation.
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500 $a Source: Dissertation Abstracts International, Volume: 67-04, Section: B, page: 1828.
500 $a Adviser: Michael Snyder.
502 $a Thesis (Ph.D.)--Yale University, 2006.
520 $a The interferons (IFNs) are important regulators of vital biological processes such as antiviral defense responses, regulation of cell proliferation, apoptosis, and immune responses. The STAT (s&barbelow;ignal t&barbelow;ransducer and a&barbelow;ctivator of t&barbelow;ranscription) family of proteins mediates the transcriptional responses to many cytokines and growth factors, including the IFNs. Much research has focused on understanding STAT activation, regulation, structure, and the phenotypic effects of their absence. However, significantly less progress has been made toward identifying the specific STAT-regulated genes crucial for mediating the biological effects of the IFNs and determining how these targets are selected. We have addressed this by identifying the binding sites and target genes of IFN-activated STATs using DNA microarrays. At the present time, DNA microarrays are the most suitable technology for the unbiased exploration of gene regulation. We have utilized a combination of different microarray designs, experimental techniques, and analysis strategies to define the DNA binding sites and target genes of STAT1 and STAT2 in humans, as well as the gene transcription events under their control. First, we combined the ChIP-chip and expression profiling microarray approaches to study the activities of IFN-alpha, IFN-gamma, STAT1, and STAT2 along human chromosome 22. These experiments revealed a large amount of previously unrecognized IFN/STAT activity on human chromosome 22, as well as introduced novel mechanisms for the regulation of STAT1 binding site selection. We have also performed full-human genome IFN-induced gene expression profiling experiments using STAT-deficient cell lines. Our results have uncovered a large number of novel IFN-up- and down-regulated genes that depend upon specific STATs for their regulation. Finally, our focused characterization of two of these novel genes led to our discovery of a STAT3-mediated mechanism of inappropriate gene regulation in B-cell lymphoma.
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650 4 $a Biology, Molecular. $3 1017719
650 4 $a Health Sciences, Immunology. $3 1017716
650 4 $a Health Sciences, Oncology. $3 1018566
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