The analysis of matrix attachment regions (MARs) associated with the lymphocyte receptors has provided a link between nuclear matrix attachment and a number of activities that regulate gene expression. We identified a nuclear matrix- associated, B cell-restricted regulator of IgH transcription, Bright. Bright binds as a tetramer to MARs necessary for matrix attachment of the IgH intronic enhancer (Emu) and the VHS107 promoter. These interactions lead to DNA bending, enhanced chromatin accessibility, and transcriptional activation. As with the nuclear matrix, transcription take place in defined subnuclear topological domains. We have identified and characterized several heteromeric interactions of Bright that provide a link between one such domain, the PML nuclear body (NB), matrix attachment and transcription of the IgH locus. We propose to extend our work by (1) further characterizing the structure, function, and expression of Bright; (2) determining the functional consequences for interactions of Bright with PML NB proteins that lead to alteration of its activity and localization; and (3) investigating the mechanism by which Bright contributes to chromatin remodeling.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA031534-21
Application #
6710126
Study Section
Allergy and Immunology Study Section (ALY)
Program Officer
Mccarthy, Susan A
Project Start
1982-03-01
Project End
2007-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
21
Fiscal Year
2004
Total Cost
$267,000
Indirect Cost
Name
University of Texas Austin
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
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