mNOSTRIN is the mouse ortholog of hNOSTRIN. Unlike hNOSTRIN, which is alternatively spliced to produce two isoforms (alpha and beta), only a single isoform of mNOSTRIN has been detected in either the nucleus or cytoplasm/membrane. Because mNOSTRIN represses its own transcription through direct binding onto its own promoter, this protein is constantly expressed in a temporally regulated pattern during differentiation of F9 embryonic carcinoma cells. In this study, we identified the specific cis-element in the mNOSTRIN regulatory region that is responsible for negative autogenous control. This element exhibits inverted dyad symmetry. Furthermore, we identified a putative bZIP motif in the middle region of mNOSTRIN, which is responsible for DNA binding, and showed that disruption of the leucine zippers abolished the DNA-binding activity of mNOSTRIN. Here, we report that a single form of mNOSTRIN functions in both the nucleus and cytoplasm/membrane. In the nucleus, mNOSTRIN acts as a transcriptional repressor by binding to the cis-element through its bZIP motif. (C) 2013 Elsevier Inc. All rights reserved.