Nitric oxide (NO) is an important signaling molecule with diverse actions in a wide variety of tissues. NO is a well-known inhibitor of cell growth, DNA replication, and expression of cell-cycle genes. The effect of NO on histone H2B expression was studied in human HEK293 cells. Cell transfection with recombinant plasmids containing the luciferase gene and fragments of the histone H2B promoter region showed that NO attenuated the expression of the reporter gene. The NO-dependent regions responsible for maximal transcriptional suppression of the H2B promoter were localized to the regions of the PPAR-binding site and the minimal promoter (-65/+42 bp from the transcription start). It was assumed that the PRAP-binding site is involved in NO-dependent transcriptional suppression of the histone H2B gene and that this mechanism is associated with NO-dependent modification of low-molecular-weight ligands of PPAR.