Estrogen-stimulated expression of CTSD depends on the cyclic recruitment of DNA-binding and other transcriptional activators. Binding sites for the DNA-binding transcriptional activators SP1, USF1 and 2 have been identified in the proximal CTSD promoter (Xing and Archer, 1998; Wang et al, 1998; Krishnan et al, 1994; Wang et al, 2001; reviewed in Safe, 2000). Other early factors that contribute to estrogen-dependent CTSD expression include the co-activator NCOA3, EP300 and MED1, a component of the mediator complex. These factors contribute to the formation of transcriptionally active chromatin and to the recruitment of RNA polymerase II (Shang et al, 2000; Bretschneider et al, 2008). Note that although these factors are shown at the CTSD promoter simultaneously, they have not all been demonstrated to form part of a single complex on an individual CTSD promoter.