Regulatory Roles of PARP-1 and Lipids in Epigenetic Mechanisms

Epigenetic modifications, reversibly controlling gene expression, are crucial for interpreting the genome under the influence of physiological factors. The basic processes (DNA methylation and histone modification, DNA accessibility, and chromatin structure) which characterize epigenetics are regulated by an orchestrated series of events. The spectrum of these events is becoming wider and wider, increasing the complexity of the interplay between the basic processes and the multiple side mechanisms responsive to environmental stimuli. The "histone code hypothesis" suggests that combinations of different histone modifications may regulate chromatin structure and transcriptional activity. Among these modifications, a crucial role is played by poly(ADP-ribosyl)ation, the reaction catalyzed by poly(ADP-ribose)polymerase-1 widely recognized as a "genome guardian" for driving the repair of damaged DNA. Increasing evidence indicates also that alterations in membrane phospholipid composition and lipid metabolism may play a role in epigenetics. Moreover, a "lipid code" has been proposed since in the nucleus a lipid fraction is present that seems tightly bound to DNA. This review will analyze these topics and their possible interplay in epigenetic regulation and discuss the relative role of nutritional and environmental challenges