Int. J. Environ. Res. Public Health 2010, 7 947 Some mechanisms of genome-regulatory effects of CRY proteins have recently been described. The schematic image of co-operation of CRY with the major cell regulatory proteins is presented in Figure 5. In Drosophila, CRY interacts with key circadian clock proteins, period and timeless (PER and TIM), in a light-dependent manner [56]. In mammals, CRY inhibits the activity of the CLOCK/BMAL1 heterodimer, which controls expression of hundreds of genes, including circadian clock regulators—genes Per and Cry [52,53]. It is believed that CLOCK/BMAL1-dependent rhythmic expression of numerous genes provides the explanation for circadian control of multiple physiological outputs [57]. Physical interaction between CRY and the PER-TIM protein complex is required for heat-mediated behavioural responses in Drosophila [56]. Taken together, these data indicates that CRY participates in regulation of various adaptive responses including responses to temperature and light variations. Figure 5. Representation of the co-operation of CRY molecule with the major cell cycle regulator-transcription factor heterodimer, CLOCK/BMAL1, transcriptional corepressors and PER proteins. (From [53], reproduced with permission from American Society for Microbiology). According to [58], CRY1 and CRY2 bind directly to BMAL1 close to its C-terminus, which has been described as a potential interaction site for an important transcriptional coactivator, the CREB-binding protein (CBP), which has intrinsic histone acetyltransferase activity. Some authors suggest that CRY controls circadian gene expression by periodic disruption of CLOCK/BMAL1 interaction with histone acetyl-transferase (HAT), which results in alteration of HAT recruitment to specific promoter regions and correspondingly the repression of circadian gene expression [59]. Later, it was shown that CRYs themselves do not act as transcriptional inhibitors, but execute their repressor function by converting the CLOCK/BMAL1 complex from a transcriptional activator to a transcriptional repressor [60]. We have further developed this concept to propose mediatory functions of the CRY as primary “epigenetic sensors” of magnetic field fluctuations. Our conception of the CRY function as magnetic field-sensitive part of the epigenetic regulatory mechanism is shown in Figure 6. As already mentioned, external magnetic fields with specific parameters may modify the functional activity of CRY. In such cases, we can expect either abolishment of the CRY repressor function and restoration of CLOCK/BMAL1 transcriptional activation function (Figure 6(c)), or an increase of CRY transcription repressor activity (not shown).