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.