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The PRH/Hex repressor protein causes nuclear retention of Groucho/TLE co-repressors

Desjobert, Cecile; Noy, Peter; Swingler, Tracey; Williams, Hannah; Gaston, Kevin; Jayaraman, Padma-Sheela

Authors

Cecile Desjobert

Peter Noy

Tracey Swingler

Hannah Williams

Kevin Gaston

Padma-Sheela Jayaraman



Abstract

The PRH (proline-rich homeodomain) [also known as Hex (haematopoietically expressed homeobox)] protein is a transcription factor that functions as an important regulator of vertebrate development and many other processes in the adult including haematopoiesis. The Groucho/TLE (transducin-like enhancer) family of co-repressor proteins also regulate development and modulate the activity of many DNA-binding transcription factors during a range of diverse cellular processes including haematopoiesis. We have shown previously that PRH is a repressor of transcription in haematopoietic cells and that an Eh-1 (Engrailed homology) motif present within the N-terminal transcription repression domain of PRH mediates binding to Groucho/TLE proteins and enables co-repression. In the present study we demonstrate that PRH regulates the nuclear retention of TLE proteins during cellular fractionation. We show that transcriptional repression and the nuclear retention of TLE proteins requires PRH to bind to both TLE and DNA. In addition, we characterize a trans-dominant-negative PRH protein that inhibits wild-type PRH activity by sequestering TLE proteins to specific subnuclear domains. These results demonstrate that transcriptional repression by PRH is dependent on TLE availability and suggest that subnuclear localization of TLE plays an important role in transcriptional repression by PRH.

Journal Article Type Article
Publication Date 2009-01
Journal Biochimica et Biophysica Acta (BBA) - Biomembranes
Print ISSN 0005-2736
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 417
Issue 1
Pages 121-132
APA6 Citation Desjobert, C., Noy, P., Swingler, T., Williams, H., Gaston, K., & Jayaraman, P. (2009). The PRH/Hex repressor protein causes nuclear retention of Groucho/TLE co-repressors. BBA - Biomembranes, 417(1), 121-132. doi:10.1042/BJ20080872
DOI https://doi.org/10.1042/BJ20080872
Publisher URL http://www.biochemj.org/content/417/1/121

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