Abstract

Regulatory sequences that influence the expression of Ig genes in late stage B cells will be investigated in this application. Based on observations that some IgH enhancer sequences, notably E-mu, can be removed from mature B cells without negatively impacting IgH expression, the determinants that enhance Ig expression in these late stage B cells needs definition. In preliminary experiments, the investigator has showed that deletion of a 3' enhancer element (3'aE) leads to loss of IgG2a expression. Further examination and definition of the control elements regulating IgH gene expression will be evaluated by site-specific deletion of the putative elements in late stage B cells and embryonic stem (ES) cells. In addition to characterizing cis-acting DNA elements in Ig gene expression, the plan is also to prepare a deletion in a gene encoding the Oct-2 transcription factor to determine if the use of this factor is or is not dispensable in late stage B cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI030653-09
Application #
2672043
Study Section
Special Emphasis Panel (ZRG2-ALY (01))
Project Start
1992-10-01
Project End
2001-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
9
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Hunter College
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Peng, Cheng; Eckhardt, Laurel A (2013) Role of the Igh intronic enhancer E? in clonal selection at the pre-B to immature B cell transition. J Immunol 191:4399-411
Yan, Yi; Pieretti, Joyce; Ju, Zhongliang et al. (2011) Homologous elements hs3a and hs3b in the 3' regulatory region of the murine immunoglobulin heavy chain (Igh) locus are both dispensable for class-switch recombination. J Biol Chem 286:27123-31
Li, Fubin; Yan, Yi; Pieretti, Joyce et al. (2010) Comparison of identical and functional Igh alleles reveals a nonessential role for Eýý in somatic hypermutation and class-switch recombination. J Immunol 185:6049-57
Li, Fubin; Eckhardt, Laurel A (2009) A role for the IgH intronic enhancer E mu in enforcing allelic exclusion. J Exp Med 206:153-67
Zhang, Buyi; Alaie-Petrillo, Adrienne; Kon, Maria et al. (2007) Transcription of a productively rearranged Ig VDJC alpha does not require the presence of HS4 in the IgH 3'regulatory region. J Immunol 178:6297-306
Yan, Yi; Park, Sung Sup; Janz, Siegfried et al. (2007) In a model of immunoglobulin heavy-chain (IGH)/MYC translocation, the Igh 3'regulatory region induces MYC expression at the immature stage of B cell development. Genes Chromosomes Cancer 46:950-9
Garrett, Francine E; Emelyanov, Alexander V; Sepulveda, Manuel A et al. (2005) Chromatin architecture near a potential 3' end of the igh locus involves modular regulation of histone modifications during B-Cell development and in vivo occupancy at CTCF sites. Mol Cell Biol 25:1511-25
Shi, X; Eckhardt, L A (2001) Deletional analyses reveal an essential role for the hs3b/hs4 IgH 3' enhancer pair in an Ig-secreting but not an earlier-stage B cell line. Int Immunol 13:1003-12
Stevens, S; Ong, J; Kim, U et al. (2000) Role of OCA-B in 3'-IgH enhancer function. J Immunol 164:5306-12
Ong, J; Stevens, S; Roeder, R G et al. (1998) 3' IgH enhancer elements shift synergistic interactions during B cell development. J Immunol 160:4896-903

Showing the most recent 10 out of 12 publications