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Molecular and Cellular Biology, May 2004, p. 3747-3756, Vol. 24, No. 9
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.9.3747-3756.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Chromosomal Proteins HMGN3a and HMGN3b Regulate the Expression of Glycine Transporter 1

Katherine L. West,1,2* Meryl A. Castellini,3 Melinda K. Duncan,3 and Michael Bustin2

Division of Cancer Sciences and Molecular Pathology, University of Glasgow, Glasgow, United Kingdom,1 Department of Biological Sciences, University of Delaware, Newark, Delaware,3 Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland2

Received 23 January 2004/ Accepted 16 February 2004

HMGN proteins promote chromatin unfolding, enhance access to nucleosomes, and modulate transcription from chromatin templates. It is not known whether they act indiscriminately as general modulators of transcription or whether they regulate specific gene expression. Here, we investigated the role of HMGN3, a recently discovered HMGN family member, in transcription in vivo. We created cell lines overexpressing HMGN3a or its splice variant, HMGN3b, and analyzed their gene expression profiles using microarrays and reverse transcriptase PCR. We found that ectopic expression of HMGN3a alters the expression of approximately 0.8% of genes. Both HMGN3a and HMGN3b upregulate the expression of the glycine transporter 1 gene (Glyt1). Glyt1 encodes a membrane transporter that regulates the glycine concentration in synaptic junctions. Both GLYT1 and HMGN3 are highly expressed in glia cells and the eye, and we show that both proteins are coexpressed in the retina. Chromatin immunoprecipitation assays showed that HMGN3 protein is recruited to a region of the Glyt1 gene encompassing the Glyt1a transcriptional start site. These results suggest that HMGN3 regulates Glyt1 expression and demonstrate that members of the HMGN family can regulate the transcription of specific genes.

* Corresponding author. Mailing address: Department of Pathology, Western Infirmary, Dumbarton Rd., Glasgow G11 6NT, United Kingdom. Phone: (44) 141 211 6329. Fax: (44) 141 337 2494. E-mail: k.west{at}clinmed.gla.ac.uk.

Molecular and Cellular Biology, May 2004, p. 3747-3756, Vol. 24, No. 9
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.9.3747-3756.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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