Abstract

The overall objective of the research proposed in this grant application is to examine the role of helix-loop-helix proteins in B-lineage development. The E2A proteins are helix-loop-helix proteins, which in B lymphocytes bind as homodimers. We have recently shown that the E2A proteins play essential roles throughout B cell development. Both E12 and E47 are required during the early stages prior to the onset of immunoglobulin (Ig) rearrangement. They have the ability to promote IgH and Ig kappa rearrangement. Finally, they are required to induce class switch recombination in activated B lineage cells. We propose to continue these studies. In particular we would investigate the relationship of E2A, EBF and Pax-5. We would examine how E2A proteins regulate Ig V(D)J recombination. We would assess the role of Id2 and Id3 in early B lineage development and examine how E2A and Id proteins are regulated during the pro-B to pre-B cell transition. We would clarify whether E12 or E47 or both are required for Ig isotype switching. Finally, we would examine how E2A protein levels are regulated in activated mature B lineage cells. Overall the dissection of the roles of E2A and Id in B cell development should help to clarify the mechanism of how HLH proteins regulate B lineage development.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA054198-14
Application #
6696901
Study Section
Allergy and Immunology Study Section (ALY)
Program Officer
Mccarthy, Susan A
Project Start
1991-04-01
Project End
2006-01-31
Budget Start
2004-02-01
Budget End
2005-01-31
Support Year
14
Fiscal Year
2004
Total Cost
$436,895
Indirect Cost

  Institution

Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Miyazaki, Masaki; Miyazaki, Kazuko; Chen, Shuwen et al. (2014) Id2 and Id3 maintain the regulatory T cell pool to suppress inflammatory disease. Nat Immunol 15:767-76
Miyazaki, Kazuko; Miyazaki, Masaki; Murre, Cornelis (2014) The establishment of B versus T cell identity. Trends Immunol 35:205-10
Guo, Chunguang; Yoon, Hye Suk; Franklin, Andrew et al. (2011) CTCF-binding elements mediate control of V(D)J recombination. Nature 477:424-30
Mercer, Elinore M; Lin, Yin C; Benner, Christopher et al. (2011) Multilineage priming of enhancer repertoires precedes commitment to the B and myeloid cell lineages in hematopoietic progenitors. Immunity 35:413-25
Miyazaki, Masaki; Rivera, Richard R; Miyazaki, Kazuko et al. (2011) The opposing roles of the transcription factor E2A and its antagonist Id3 that orchestrate and enforce the naive fate of T cells. Nat Immunol 12:992-1001
Mercer, Elinore M; Lin, Yin C; Murre, Cornelis (2011) Factors and networks that underpin early hematopoiesis. Semin Immunol 23:317-25
Lin, Yin C; Jhunjhunwala, Suchit; Benner, Christopher et al. (2010) A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate. Nat Immunol 11:635-43
Roberts, V J; van Dijk, M A; Murre, C (1995) Localization of Pbx1 transcripts in developing rat embryos. Mech Dev 51:193-8
Bain, G; Maandag, E C; Izon, D J et al. (1994) E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements. Cell 79:885-92
van Dijk, M A; Murre, C (1994) extradenticle raises the DNA binding specificity of homeotic selector gene products. Cell 78:617-24

Showing the most recent 10 out of 12 publications