HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schweitzer, B. L. Articles by DeKoter, R. P. Search for Related Content PubMed PubMed Citation Articles by Schweitzer, B. L. Articles by DeKoter, R. P.

Spi-C Has Opposing Effects to PU.1 on Gene Expression in Progenitor B Cells¹

Brock L. Schweitzer^*, Kelly J. Huang^*, Meghana B. Kamath^*, Alexander V. Emelyanov, Barbara K. Birshtein and Rodney P. DeKoter^2,*

^* Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267; and Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461

The Ets transcription factor Spi-C, expressed in B cells and macrophages, is closely related to PU.1 and has the ability to recognize the same DNA consensus sequence. However, the function of Spi-C has yet to be determined. The purpose of this study is to further examine Spi-C activity in B cell development. First, using retroviral vectors to infect PU.1^–/– fetal liver progenitors, Spi-C was found to be inefficient at inducing cytokine-dependent proliferation and differentiation of progenitor B (pro-B) cells or macrophages relative to PU.1 or Spi-B. Next, Spi-C was ectopically expressed in fetal liver-derived, IL-7-dependent pro-B cell lines. Wild-type (WT) pro-B cells ectopically expressing Spi-C (WT-Spi-C) have several phenotypic characteristics of pre-B cells such as increased CD25 and decreased c-Kit surface expression. In addition, WT-Spi-C pro-B cells express increased levels of IgH sterile transcripts and reduced levels of expression and transcription of the FcRIIb gene. Gel-shift analysis suggests that Spi-C, ectopically expressed in pro-B cells, can bind PU.1 consensus sites in the IgH intronic enhancer and FcRIIb promoter. Transient transfection analysis demonstrated that PU.1 functions to repress the IgH intronic enhancer and activate the FcRIIb promoter, while Spi-C opposes these activities. WT-Spi-C pro-B cells have reduced levels of dimethylation on lysine 9 of histone H3 within the IgH 3' regulatory region, indicating that Spi-C can contribute to removal of repressive features in the IgH locus. Overall, these studies suggest that Spi-C may promote B cell differentiation by modulating the activity of PU.1-dependent genes.

This article has been cited by other articles:

				R. P. DeKoter, B. L. Schweitzer, M. B. Kamath, D. Jones, H. Tagoh, C. Bonifer, D. A. Hildeman, and K. J. Huang Regulation of the Interleukin-7 Receptor {alpha} Promoter by the Ets Transcription Factors PU.1 and GA-binding Protein in Developing B Cells J. Biol. Chem., May 11, 2007; 282(19): 14194 - 14204. [Abstract] [Full Text] [PDF]