Nucleic Acids Research Advance Access originally published online on June 22, 2007
Nucleic Acids Research 2007 35(14):4583-4596; doi:10.1093/nar/gkm477
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Nucleic Acids Research, 2007, Vol. 35, No. 14 4583-4596
© 2007 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.
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Delta–Notch—and then? Protein interactions and proposed modes of repression by Hes and Hey bHLH factors
Physiological Chemistry I, Biocenter, Theodor-Boveri-Institute, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany
*To whom correspondence should be addressed. Tel: +49 931 888 4158; Fax: +49 931 888 4150; Email: gessler{at}biozentrum.uni-wuerzburg.de
Received March 12, 2007. Revised May 30, 2007. Accepted May 31, 2007.
Hes and Hey genes are the mammalian counterparts of the Hairy and Enhancer-of-split type of genes in Drosophila and they represent the primary targets of the Delta–Notch signaling pathway. Hairy-related factors control multiple steps of embryonic development and misregulation is associated with various defects. Hes and Hey genes (also called Hesr, Chf, Hrt, Herp or gridlock) encode transcriptional regulators of the basic helix-loop-helix class that mainly act as repressors. The molecular details of how Hes and Hey proteins control transcription are still poorly understood, however.
Proposed modes of action include direct binding to N- or E-box DNA sequences of target promoters as well as indirect binding through other sequence-specific transcription factors or sequestration of transcriptional activators. Repression may rely on recruitment of corepressors and induction of histone modifications, or even interference with the general transcriptional machinery. All of these models require extensive protein–protein interactions. Here we review data published on protein–protein and protein–DNA interactions of Hairy-related factors and discuss their implications for transcriptional regulation. In addition, we summarize recent progress on the identification of potential target genes and the analysis of mouse models.
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