Abstract: In development, epigenetic mechanisms such as DNA methylation have been suggested to provide a cellularmemoryto maintain multipotency but also stabilize cell fate decisions and direct lineage restriction. In this study, we set out to characterize changes in DNA methylation and gene expression during granulopoiesis using 4 distinct cell populations ranging from the oligopotent common myeloid progenitor stage to terminally differentiated neutrophils. We observed that differentially methylated sites (DMSs) generally show decreased methylation during granulopoiesis. Methylation appears to change at specific differentiation stages and overlap with changes in transcription and activity of key hematopoietic transcription factors. DMSs were preferentially located in areas distal to CpG islands and shores. Also, DMSs were overrepresented in enhancer elements and enriched in enhancers that become active during differentiation.Overall, this studydepicts in detail the epigenetic and transcriptional changes that occur during granulopoiesis and supports the role of DNA methylation as a regulatory mechanism in blood cell differentiation.

Abstract: Understanding the biophysical basis of animal magnetoreception has been one of the greatest challenges in sensory biology. Recently it was discovered that the light-dependent magnetic sense of Drosophila melanogaster is mediated by the ultraviolet (UV)-A/blue light photoreceptor cryptochrome (Cry). Here we show, using a transgenic approach, that the photoreceptive, Drosophila-like type 1 Cry and the transcriptionally repressive, vertebrate-like type 2 Cry of the monarch butterfly (Danaus plexippus) can both function in the magnetoreception system of Drosophila and require UV-A/blue light (wavelength below 420 nm) to do so. The lack of magnetic responses for both Cry types at wavelengths above 420 nm does not fit the widely held view that tryptophan triad-generated radical pairs mediate the ability of Cry to sense a magnetic field. We bolster this assessment by using a mutant form of Drosophila and monarch type 1 Cry and confirm that the tryptophan triad pathway is not crucial in magnetic transduction. Together, these results suggest that animal Crys mediate light-dependent magnetoreception through an unconventional photochemical mechanism. This work emphasizes the utility of Drosophila transgenesis for elucidating the precise mechanisms of Cry-mediated magnetosensitivity in insects and also in vertebrates such as migrating birds.

Abstract: A number of epidemiological studies have suggested that exposure to 50/60-Hz magnetic fields (MF) from power lines and electrical equipment may be associated with a modestly increased incidence of various types of cancer. Laboratory studies have indicated that nonionizing radiation has no mutagenic effect, i.e. does not initiate cancer. Thus, if 50/60-Hz MF are truly associated with an increased risk of cancer, then these fields must act as a promoter or co-promoter of cancer in cells that have already been initiated. This paper reviews the evidence produced by animal studies. As shown in this review, the available animal data on 50/60-Hz MF exposures seem to indicate that intermediate MF exposure exerts co-promoting effects in different tumor models, particularly cocarcinogenesis models of breast cancer, while chronic (up to life-time) exposure may exert promoting effects on “spontaneous” development of certain tumors. The tumor promoting or co-promoting effects of 50/60-Hz MF exposure found in several animal studies could relate to actions of MF on gene expression, immune surveillance, and Ca2+ homeostasis as demonstrated by in vitro experiments in cell cultures. However, the most plausible evidence for an in vivo effect of MF exposure which could be related to tumor promotion is reduction of circulating levels of melatonin, i.e. a hormone which is inhibitory to the growth of a wide range of cancers, particularly breast cancer. Animal studies have shown that 50-Hz MF exposure at flux densities as low as 0.3-1 mu Tesla significantly reduces nocturnal melatonin levels in plasma. While decrease of melatonin levels alone could explain tumor promoting or co-promoting effects of MF exposure, recent data indicate that MF exposure also impairs the effects of melatonin at the cellular level. Thus, the oncostatic effect of melatonin on cell proliferation of a human breast cancer cell line was antagonized by 60-Hz MF exposure at a flux density of about 1 mu Tesla. All these data indicate that interactions between 50/60-HZ MF exposure and melatonin may be the key mechanism of any carcinogenic effects. Although the existing experimental evidence is still insufficient for discerning a cause-effect relationship for MF exposure and human disease or injury, it does suggest the need for further laboratory research under well-defined laboratory exposure conditions to allow for a realistic assessment of the possible health risks and their magnitude.