Integration of syntactic and semantic properties of the DNA code reveals chromosomes as thermodynamic machines converting energy into information.

Understanding genetic regulation is a problem of fundamental importance. Recent studies have made it increasingly evident that, whereas the cellular genetic regulation system embodies multiple disparate elements engaged in numerous interactions, the central issue is the genuine function of the DNA molecule as information carrier. Compelling evidence suggests that the DNA, in addition to the digital information of the linear genetic code (the semantics), encodes equally important continuous, or analog, information that specifies the structural dynamics and configuration (the syntax) of the polymer. These two DNA information types are intrinsically coupled in the primary sequence organisation, and this coupling is directly relevant to regulation of the genetic function. In this review, we emphasise the critical need of holistic integration of the DNA information as a prerequisite for understanding the organisational complexity of the genetic regulation system.