Functional elements and regulatory influence of the T cell receptor alpha locus control region.
Item
-
Title
-
Functional elements and regulatory influence of the T cell receptor alpha locus control region.
-
Identifier
-
AAI3325402
-
identifier
-
3325402
-
Creator
-
Klein, Janette Gomos.
-
Contributor
-
Adviser: Benjamin D. Ortiz
-
Date
-
2008
-
Language
-
English
-
Publisher
-
City University of New York.
-
Subject
-
Biology, Molecular | Biology, Genetics
-
Abstract
-
Gene regulation is an essential component in biological processes especially in complex mammalian genomes where loci have differentially regulated genes. An important part of ensuring proper gene regulation are components that activate and maintain separate domains allowing for specific gene expression profiles.;Locus control regions (LCRs) are non-coding DNA elements that regulate gene expression. LCRs provide high-level, position-independent expression to a randomly integrated transgene in a tissue specific manner. It achieves this through DNA sequences supporting multiple activities that enhance transcription and protect the expression of a transgene locus from integration site-dependent position effects. Except for elements with classical enhancer function, most key elements of the LCR activity are not well understood.;These studies used randomly integrated reporter transgene systems to identify functional elements and assess the role of the LCR within the mouse T cell receptor (TCR) alpha/Dad1 gene locus. Our investigations identified CTCF-independent regions that specifically help suppresses position effects due to random integration. Interestingly, we also found that LCR activity is orientation independent even though the endogenous gene downstream of it is ubiquitously active. In addition, our studies revealed separate 5' and 3' directed regulatory activities of the LCR. Further studies using a large, more endogenous, chromatin-like bacterial artificial chromosome (BAC) containing reporter genes flanking the LCR was also designed to further address some functions of gene regulation in this complex locus.
-
Type
-
dissertation
-
Source
-
PQT Legacy CUNY.xlsx
-
degree
-
Ph.D.
