ARID (AT- Rich Interaction Domain) transcription factors have been implicated in chromatin remodeling and growth deregulation. Of the 13 members of the ARID family, two are termed eARIDs because they show extended (e) identity beyond the ARID DNA binding domain: Bright (for B cell specific regulator of IgH transcription) and Bdp (for Bright-Dri-like protein). Bright functions as a positive transcriptional activator of specific motifs (P sites) within nuclear matrix associated regions (MARs) flanking the IgH intronic enhancer (Em) and 5' to the V1 member of the VH $107 family. In human (h) and mouse (m) B cell differentiation, Bright is restricted to early preB and germinal center B cells. Little is known about Bdp in either species.
Aim 1 proposes a full characterization of Bdp expression, function, and localization relative to Bright.
In Aim 2 we propose to identify and validate genes in additional to IgH that are activated by the eARIDs. Our initial focus will include 5 targets that define a potential role for Bright in cell survival. There have been no ARID knockouts reported. Conventional targeted disruption of the Bright gene in mice leads to embryonic lethality (Progress Report).
In Aim 3, we propose a conditional knockout approach for eliminating Bright only in B cells. We will evaluate Bright null mice in the context of normal and malignant B cell biology and with regard to the developmental and repertoire dysfunction proposed for Bright in X-linked immunodeficiency disease. We propose to create Bdp null mice using one of the above strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI064886-03
Application #
7009961
Study Section
Immunobiology Study Section (IMB)
Program Officer
Nasseri, M Faraz
Project Start
2004-08-01
Project End
2009-01-31
Budget Start
2006-02-01
Budget End
2007-01-31
Support Year
3
Fiscal Year
2006
Total Cost
$292,950
Indirect Cost
Name
University of Texas Austin
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
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Mathur, Shawn; Schmidt, Christian; Das, Chhaya et al. (2006) Open Access and beyond. Mol Cancer 5:35
Kim, Dongkyoon; Tucker, Philip W (2006) A regulated nucleocytoplasmic shuttle contributes to Bright's function as a transcriptional activator of immunoglobulin genes. Mol Cell Biol 26:2187-201