Studies of DNA methylation from fungi, plants, and animals indicate that gene body methylation is ancient and highly conserved in eukaryotic genomes, but its role has not been clearly defined. It has been postulated that regulation of alternative splicing of transcripts was an original function of DNA methylation, but a direct experimental test of the effect of methylation on alternative slicing at the whole genome level has never been performed. To do this, we developed a unique method to administer RNA interference (RNAi) in a high-throughput and noninvasive manner and then used it to knock down the expression of DNA methyltransferase 3 (dnmt3), which is required for de novo DNA methylation. We chose the honey bee (Apis mellifera) for this test because it has recently emerged as an important model organism for studying the effects of DNA methylation on development and social behavior, and DNA methylation in honey bees is predominantly on gene bodies. Here we show that dnmt3 RNAi decreased global genomic methylation level as expected and in addition caused widespread and diverse changes in alternative splicing in fat tissue. Four different types of splicing events were affected by dnmt3 gene knockdown, and change in two types, exon skipping and intron retention, was directly related to decreased methylation. These results demonstrate that one function of gene body DNA methylation is to regulate alternative splicing.epigenetics | gene regulation | gene silencing | insect

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Implantable medical devices are widely used for monitoring and treatment of severe diseases. In particular, an implantable cardiac pacemaker is the most effective therapeutic device for treating bradyrhythmia, however its surgical replacement is inevitable every 5–12 years due to the limited life of the built-in battery. Although several approaches of energy harvesting have been explored in this decade for powering cardiac pacemakers, the modern, commercial, and full-function pacemaker has never been powered effectively yet. Here, we report an integrated strategy for directly powering a modern and full-function cardiac pacemaker, which can pace the porcine heart in vivo by harvesting the natural energy of a heartbeat, without using any external energy storage element. The generator includes an elastic skeleton and two piezoelectric composites, which could generate a high-output current of 15 μA in vivo over state-of-the-art performance. This study makes an impressive step toward fabricating a self-powered cardiac pacemaker and resolving the power issue of implantable medical devices by piezoelectric harvesting technology.

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