US EPA

1554362 

Journal Article 

[Role of transcription factors binding sites in no-mediated histone H2B promoter repression] 

Pankratova, EV; Manuĭlova, EA; Stepchenko, AG 

2009 

1 

Molekulyarnaya Biologiya
ISSN: 0026-8984 

43 

2 

368-373 

rus 

19425504 

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 implicated genes. In this study we analyzed the effect of NO on histone H2B expression in human HEK 293 cells. Using cell transfection with a plasmid expressing reporter gene under the control of histone H2B promoter, we showed that NO markedly attenuated the expression of the reporter gene indicating that NO inhibits the expression of the histone H2B gene at the level of transcription. Deletion and mutational analysis of the H2B gene promoter showed that the PPAR binding site and the region of "minimal" promoter (-65/+42 bp from transcription start) was an important for NO-dependent repression of histone H2B transcription. The peroxisome proliferator-activated receptor (PPAR) is a ligand-activated transcription factor that plays an important role in the regulation of lipid metabolism, cellular proliferation and inflammatory responses. It seems likely that NO-mediated H2B gene repression depends on modifications of endogenous PPAR ligands.