Nucleic Acids Research Advance Access originally published online on December 2, 2008
Nucleic Acids Research 2009 37(2):431-440; doi:10.1093/nar/gkn955
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Nucleic Acids Research, 2009, Vol. 37, No. 2 431-440
© 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.
Gene regulation, Chromatin and Epigenetics |
Dynamic interaction between WT1 and BASP1 in transcriptional regulation during differentiation
Faculty of Life Sciences, The Michael Smith Building University of Manchester Oxford Road, Manchester M13 9PT, UK
*To whom correspondence should be addressed. Tel: +44 0161 275 5758; Fax: +44 0161 275 5082; Email: stefan.roberts{at}manchester.ac.uk
Received September 30, 2008. Revised November 10, 2008. Accepted November 10, 2008.
The Wilms tumour suppressor protein WT1 plays a central role in the development of the kidney and also other organs. WT1 can act as a transcription factor with highly context-specific activator and repressor functions. We previously identified Brain Acid Soluble Protein 1 (BASP1) as a transcriptional cosuppressor that can block the transcriptional activation function of WT1. WT1 and BASP1 are co-expressed during nephrogenesis and both proteins ultimately become restricted to the podocyte cells of the adult kidney. Here, we have analysed the WT1/BASP1 complex in a podocyte precursor cell line that can be induced to differentiate. Chromatin immunoprecipitation revealed that WT1 and BASP1 occupy the promoters of the Bak, c-myc and podocalyxin genes in podocyte precursor cells. During differentiation-dependent upregulation of podocalyxin expression BASP1 occupancy of the podocalyxin promoter is reduced compared to that of WT1. In contrast, the repressive WT1/BASP1 occupancy of the c-myc and Bak promoters is maintained and these genes are downregulated during the differentiation process. We provide evidence that the regulation of BASP1 promoter occupancy involves the sumoylation of BASP1. Our results reveal a dynamic cooperation between WT1 and BASP1 in the regulation of gene expression during differentiation.
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