Targeting a Transcriptional Activator Induces Changes in Large-Scale Chromatin Structure and Nuclear Positioning
Tumbar, Tudorita
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https://hdl.handle.net/2142/85496
Description
Title
Targeting a Transcriptional Activator Induces Changes in Large-Scale Chromatin Structure and Nuclear Positioning
Author(s)
Tumbar, Tudorita
Issue Date
2000
Doctoral Committee Chair(s)
Belmont, Andrew S.
Department of Study
Biophysics and Computational Biology
Discipline
Biophysics and Computational Biology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Cell
Language
eng
Abstract
This study addresses the relationship between transcriptional activation and large-scale chromatin structure and nuclear positioning. We have used an artificial system to target large amounts of the very strong viral transcriptional activator, VP16, to specific chromosome sites. The rationale of this approach is to use this exaggerated system to amplify effects on large-scale chromatin to the extent where they could be easily analyzed. We have demonstrated a re-programming of the cell-cycle dependent sequence of intranuclear positioning of a chromosome site, by the targeting of VP16 transcriptional activator. For a different chromosome site we describe a striking remodeling of chromatin structure including unfolding of a 90 Mbp heterochromatic chromosome arm into an extended 25--40 mum chromonema fiber, remodeling of this fiber in a novel subnuclear domain, and propagation of unfolding over hundreds of kilobase pairs. These changes occurred even in the absence of transcription and were accompanied by an increase in transcriptional activation, localized histone hyperacetylation, and recruitment of three histone acetyltransferases. Based on the observed propagation of changes in large-scale chromatin structure, we suggest a possible rationale for the observed clustering of housekeeping genes within Mbp-sized chromosome sites.
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