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J. Biol. Chem., Vol. 282, Issue 17, 12439-12449, April 27, 2007

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Nucleolin Regulates Gene Expression in CD34-positive Hematopoietic Cells^*

From the Institute of Transplantation Diagnostics and Cellular Therapeutics, Heinrich Heine University Medical Center, 40225 Düsseldorf, Germany

CD34 glycoprotein in human hematopoiesis is expressed on a subset of progenitor cells capable of self-renewal, multilineage differentiation, and hematopoietic reconstitution. Nucleolin is an abundant multifunctional phosphoprotein of growing eukaryotic cells, involved in regulation of gene transcription, chromatin remodeling, and RNA metabolism, whose transcripts are enriched in murine hematopoietic stem cells, as opposed to differentiated tissue. Here we show that, in human CD34-positive hematopoietic cells, nucleolin activates endogenous CD34 and Bcl-2 gene expression, and cell surface CD34 protein expression is thereby enhanced by nucleolin. Nucleolin-mediated activation of CD34 gene transcription results from direct sequence-specific interactions with the CD34 promoter region. Nucleolin expression prevails in CD34-positive cells mobilized into peripheral blood (PB), as opposed to CD34-negative peripheral blood mononuclear cells (PBMCs). Therefore, in intact CD34-positive mobilized PB cells, a recruitment of nucleolin to the CD34 promoter region takes place, accompanied by nucleosomal determinants of gene activity, which are absent from the CD34 promoter region in CD34-negative PBMCs. Our data show that nucleolin acts as a component of the gene regulation program of CD34-positive hematopoietic cells and provide further insights into processes by which human CD34-positive hematopoietic stem/progenitor cells are maintained.

Received for publication, August 22, 2006 , and in revised form, January 16, 2007.

^* This work was funded by research grants from the Research Commission of the Medical Faculty of the University of Düsseldorf and the MSWF of the State NRW (to E. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S3.

¹ To whom correspondence should be addressed: Institute of Transplantation Diagnostics and Cellular Therapeutics, Heinrich Heine University Medical Center, Moorenstr. 5, Bldg. 14.80, 40225 Düsseldorf, Germany. Tel.: 49-211-811-9534; Fax: 49-211-811-9147; E-mail: Edgar.Grinstein{at}web.de.

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