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Nucleic Acids Research Advance Access originally published online on May 20, 2008
Nucleic Acids Research 2008 36(11):3802-3818; doi:10.1093/nar/gkn271
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Nucleic Acids Research, 2008, Vol. 36, No. 11 3802-3818
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

In vivo identification of novel STAT5 target genes

Beth Basham1, Manjiri Sathe1, Jeffrey Grein1, Terrill McClanahan1, Annalisa D’Andrea2, Emma Lees1 and Anne Rascle1,3,*

1Schering-Plough Biopharma (formerly DNAX Research Inc.), 901 California Avenue, Palo Alto, CA 94304, 2Biosciences Division, SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA and 3Institute for Molecular and Cellular Anatomy, University of Regensburg, Universitaetsstrasse 31, 93053 Regensburg, Germany

*To whom correspondence should be addressed. Tel: +49 (0)941 943 2862; Fax: +49 (0)941 943 2868; Email: anne.rascle{at}vkl.uni-regensburg.de

Received February 6, 2008. Revised April 22, 2008. Accepted April 23, 2008.

STAT5A and STAT5B proteins belong to the family of signal transducers and activators of transcription. They are encoded by two separate genes with 91% identity in their amino acid sequences. Despite their high degree of conservation, STAT5A and STAT5B exert non-redundant functions, resulting at least in part from differences in target gene activation. To better characterize the differential contribution of STAT5A and STAT5B in gene regulation, we performed single or double knockdown of STAT5A and STAT5B using small interfering RNA. Subsequent gene expression profiling and RT-qPCR analyses of IL-3-stimulated Ba/F3-β cells led to the identification of putative novel STAT5 target genes. Chromatin immunoprecipitation assays analyzing the corresponding gene loci identified unusual STAT5 binding sites compared to conventional STAT5 responsive elements. Some of the STAT5 targets identified are upregulated in several human cancers, suggesting that they might represent potential oncogenes in STAT5-associated malignancies.


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