Abstract

Nuclear matrix associating regions (MARs) have been implicated in transcriptional control of several genes, including the immunoglobulin heavy chain (IgH). The MARs flanking the IgH intronic enhancer (Em) are the targets of positive and negative regulators identified by this investigator. Both factors partition to the nuclear matrix in cell-type, developmental stage-restricted fashions: The positive regulator in mature/Ig-secreting B cells and the negative regulator in non-B cells. The differential occupancy of these two factors is hypothesized to contribute to enhancer control, perhaps by regulating nuclear matrix attachment and/or chromatin structure. In this model the MARs function as a genetic switch, contributing to Em activation in B cells and Em repression in non-B cells. Through a series of biochemical and genetic approaches the investigator proposes to further characterize these factors and their MAR interactions, to study the mechanism of the proposed switch, and to understand the consequences upon B cell lineage development and differentiation.
In Aim 1 the structure, function and expression of Bright will be further characterized.
In Aim 2 a similar analysis will be performed on the Cux and 40kd proteins.
In Aim 3 the mechanism of the genetic switch involving these factors, and the role of MARs in this process will be investigated.
In Aim 4 the consequences of the genetic switch on Emu cell type restriction and B lineage development will be investigated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA031534-16
Application #
2667855
Study Section
Experimental Immunology Study Section (EI)
Program Officer
Mccarthy, Susan A
Project Start
1982-03-01
Project End
2001-02-28
Budget Start
1998-03-01
Budget End
1999-02-28
Support Year
16
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of Texas Austin
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
City
Austin
State
TX
Country
United States
Zip Code
78712

  Publications

Warren, Junco S; Tracy, Christopher M; Miller, Mickey R et al. (2018) Histone methyltransferase Smyd1 regulates mitochondrial energetics in the heart. Proc Natl Acad Sci U S A 115:E7871-E7880
Nie, Hui; Rathbun, Gary; Tucker, Haley (2017) Smyd1C Mediates CD8 T Cell Death via Regulation of Bcl2-Mediated Restriction of outer Mitochondrial Membrane Integrity. J Cell Signal 2:
Rhee, Catherine; Edwards, Melissa; Dang, Christine et al. (2017) ARID3A is required for mammalian placenta development. Dev Biol 422:83-91
Rhee, Catherine; Kim, Jonghwan; Tucker, Haley O (2017) Transcriptional Regulation of the First Cell Fate Decision. J Dev Biol Regen Med 1:
Kim, Dongkyoon; Schmidt, Christian; Brown, Mark A et al. (2017) Competitive Promoter-Associated Matrix Attachment Region Binding of the Arid3a and Cux1 Transcription Factors. Diseases 5:
Li, Hanjun; Liu, Pei; Xu, Shuqin et al. (2017) FOXP1 controls mesenchymal stem cell commitment and senescence during skeletal aging. J Clin Invest 127:1241-1253
Li, Shanru; Morley, Michael; Lu, MinMin et al. (2016) Foxp transcription factors suppress a non-pulmonary gene expression program to permit proper lung development. Dev Biol 416:338-46
Woodworth, Mollie B; Greig, Luciano C; Liu, Kevin X et al. (2016) Ctip1 Regulates the Balance between Specification of Distinct Projection Neuron Subtypes in Deep Cortical Layers. Cell Rep 15:999-1012
Huang, Ching-Jung; Das, Utsab; Xie, Weijun et al. (2016) Altered stoichiometry and nuclear delocalization of NonO and PSF promote cellular senescence. Aging (Albany NY) 8:3356-3374
Kim, Peter Geon; Canver, Matthew C; Rhee, Catherine et al. (2016) Interferon-? signaling promotes embryonic HSC maturation. Blood 128:204-16

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