Oocytes display a maternal-specific gene expression profile, which is switched to a zygotic profile when a haploid set of chromatin is passed on to the fertilized egg that develops into an embryo. The mechanism underl...Oocytes display a maternal-specific gene expression profile, which is switched to a zygotic profile when a haploid set of chromatin is passed on to the fertilized egg that develops into an embryo. The mechanism underlying this transcription reprogramming is currently unknown. Here we demonstrate that by the time when transcription is shut down in germinal vesicle oocytes, a range of general transcription factors and transcriptional regulators are dissociated from the chromatin. The global dissociation of chromatin factors （CFs） disrupts physical contacts between the chromatin and CFs and leads to erasure of the maternal transcription program at the functional level. Critical transcription factors and regulators remain separated from chromatin for a prolonged period, and become re-associated with chromatin shortly after pronuclear formation. This is followed temporally by the re-establishment of nuclear functions such as DNA replication and transcription. We propose that the maternal transcription program is erased during oogenesis to generate a relatively naive chromatin and the zygotic transcription program is rebuilt de novo after fertilization. This process is termed as the ＂erase-and-rebuild＂ process, which is used to reset the transcription program, and most likely other nuclear processes as well, from a maternal one to that of the embryo. We further show in the accompanying paper （Gao T, et al., Cell Res 2007; 17：135-150.） that the same strategy is also employed to reprogram transcriptional profiles in somatic cell nuclear transfer and parthenogenesis, suggesting that this model is universally applicable to all forms of transcriptional reprogramming during early embryogenesis. Displacement of CFs from chromatin also offers an explanation for the phenomenon of transcription silence during the maternal to zygotic transition.展开更多
Obesity, as a chronic condition, has been a serious public health issue over the last decades both in the affluent Western world and developing countries. As reported, the risk of several serious diseases increases wi...Obesity, as a chronic condition, has been a serious public health issue over the last decades both in the affluent Western world and developing countries. As reported, the risk of several serious diseases increases with weight gain, including type 2 diabetes,coronary heart disease, cancer, and respiratory diseases. In addition to lifestyle modifications, pharmacotherapy has become an important strategy to control weight gain. However, most of the anti-obesity drugs often show poor outcome for weight-loss and cause severe adverse effects. This review surveys recent advances in nanomedicine as an emerging strategy for obesity treatment with an emphasis on the enhanced therapeutic efficiency and minimized side effects. The insights for future development are also discussed.展开更多
文摘Oocytes display a maternal-specific gene expression profile, which is switched to a zygotic profile when a haploid set of chromatin is passed on to the fertilized egg that develops into an embryo. The mechanism underlying this transcription reprogramming is currently unknown. Here we demonstrate that by the time when transcription is shut down in germinal vesicle oocytes, a range of general transcription factors and transcriptional regulators are dissociated from the chromatin. The global dissociation of chromatin factors （CFs） disrupts physical contacts between the chromatin and CFs and leads to erasure of the maternal transcription program at the functional level. Critical transcription factors and regulators remain separated from chromatin for a prolonged period, and become re-associated with chromatin shortly after pronuclear formation. This is followed temporally by the re-establishment of nuclear functions such as DNA replication and transcription. We propose that the maternal transcription program is erased during oogenesis to generate a relatively naive chromatin and the zygotic transcription program is rebuilt de novo after fertilization. This process is termed as the ＂erase-and-rebuild＂ process, which is used to reset the transcription program, and most likely other nuclear processes as well, from a maternal one to that of the embryo. We further show in the accompanying paper （Gao T, et al., Cell Res 2007; 17：135-150.） that the same strategy is also employed to reprogram transcriptional profiles in somatic cell nuclear transfer and parthenogenesis, suggesting that this model is universally applicable to all forms of transcriptional reprogramming during early embryogenesis. Displacement of CFs from chromatin also offers an explanation for the phenomenon of transcription silence during the maternal to zygotic transition.
基金supported by the grant from Sloan Research Fellowship
文摘Obesity, as a chronic condition, has been a serious public health issue over the last decades both in the affluent Western world and developing countries. As reported, the risk of several serious diseases increases with weight gain, including type 2 diabetes,coronary heart disease, cancer, and respiratory diseases. In addition to lifestyle modifications, pharmacotherapy has become an important strategy to control weight gain. However, most of the anti-obesity drugs often show poor outcome for weight-loss and cause severe adverse effects. This review surveys recent advances in nanomedicine as an emerging strategy for obesity treatment with an emphasis on the enhanced therapeutic efficiency and minimized side effects. The insights for future development are also discussed.
