Chromatin Structure of the Human NK Cells Perforin Gene Promoter

Innate immunity plays a vital role in host defense against viral infection and tumor development. Natural Killer (NK)cells are important for the earliest stage of immuneresponse, which occurs without prior sensitization. NK cells have the ability to kill malignant or infected cellsby releasing cytotoxic proteins contained in their cytoplasmic granules. . One of these proteins is the perforin which is responsible for forming pores in the target cell membrane. Although it is believed that the control of perforin expression occurs at the transcriptional level, the molecular mechanisms responsible for that control have not been completely characterized. Our aim is to understand whether this control is somehow related to the chromatin organization of its promoter. We started defining the chromatin organization of perforin promoter using NK cells derived from peripheral blood of healthy individuals: preliminary results indicate that the promoter region spanning the gamma-interferron responsive element is occupied by a positioned nucleosome particle. We are currently analyzing the chromatin structure of the perforin promoter following activation by cytokines treatment of the in vitro cultured cells. Moreover, a similar study has been undertaken on the promoter of the gamma-interferon gene.