Brown adipose tissue(BAT)plays a key role in thermogenesis during acute cold exposure.However,it remains unclear how BAT is prepared to rapidly turn on thermogenic genes.Here,we show that damage-specific DNA binding p...Brown adipose tissue(BAT)plays a key role in thermogenesis during acute cold exposure.However,it remains unclear how BAT is prepared to rapidly turn on thermogenic genes.Here,we show that damage-specific DNA binding protein 1(DDB1)mediates the rapid transcription of thermogenic genes upon acute cold exposure.Adipose-or BAT-specific Ddb1 knockout mice show severely whitened BAT and significantly decreased expression of thermogenic genes.These mice develop hypothermia when subjected to acute cold exposure at 4℃ and partial lipodystrophy on a high-fat diet due to deficiency in fatty acid oxidation.Mechanistically,DDB1 binds the promoters of Ucp1 and Ppargc1a and recruits positive transcriptional elongation factor b(P-TEFb)to release promoter-proximally paused RNA polymerase II(Pol II),thereby enabling rapid and synchronized transcription of thermogenic genes upon acute cold exposure.Our findings have thus provided a regulatory mechanism of how BAT is prepared to respond to acute cold challenge.展开更多
Dear Editor,The intestinal epithelium is a rapidly self-renew-ing tissue for absorbing nutrients and providing bar-rier functions,and its homeostasis is orchestrated by several signaling pathways(Vermeulen and Snip-pe...Dear Editor,The intestinal epithelium is a rapidly self-renew-ing tissue for absorbing nutrients and providing bar-rier functions,and its homeostasis is orchestrated by several signaling pathways(Vermeulen and Snip-pert,2014;Zhu et al.,2021).Growing evidence dem-onstrates the importance of cell cycle regulation in intestinal homeostatic maintenance(McKernan and Egan,2015).Here,we report that the E3 ubiquitin ligase adaptor DDB1(Damaged DNA Binding Protein 1)is highly expressed in the intestinal epithelium and regulates the intestinal homeostasis by preventing cell cycle arrest.展开更多
利用RNA干涉技术构建水稻DDB1(Damaged DNA binding protein 1)基因不同启动子驱动植物表达载体,DDB1-RNAi和DDB1-glu-RNAi.通过根癌农杆菌介导转入水稻愈伤,经组织培养成功获得转基因植株.半定量RT-PCR分析显示,与野生型植株相比,两组...利用RNA干涉技术构建水稻DDB1(Damaged DNA binding protein 1)基因不同启动子驱动植物表达载体,DDB1-RNAi和DDB1-glu-RNAi.通过根癌农杆菌介导转入水稻愈伤,经组织培养成功获得转基因植株.半定量RT-PCR分析显示,与野生型植株相比,两组转基因植株幼叶内DDB1的表达量均有不同程度的降低.花粉染色结果显示,转基因植株花粉染色异常,败育率高;植株表现出明显的雄性半不育;秕谷率均有不同程度的提高;并且以上表型在DDB1-RNAi转基因植株中均比在DDB1-glu-RNAi转基因植株中明显.因此,推断DDB1基因与水稻的生殖发育有着密切的关系.展开更多
基金This work was supported by the National Key R&D Program of China(2020YFA0803601)the National Natural Science Foundation of China(32125022 and 32101046)the China Postdoctoral Science Foundation(2019M661348 and 2020T130115).
文摘Brown adipose tissue(BAT)plays a key role in thermogenesis during acute cold exposure.However,it remains unclear how BAT is prepared to rapidly turn on thermogenic genes.Here,we show that damage-specific DNA binding protein 1(DDB1)mediates the rapid transcription of thermogenic genes upon acute cold exposure.Adipose-or BAT-specific Ddb1 knockout mice show severely whitened BAT and significantly decreased expression of thermogenic genes.These mice develop hypothermia when subjected to acute cold exposure at 4℃ and partial lipodystrophy on a high-fat diet due to deficiency in fatty acid oxidation.Mechanistically,DDB1 binds the promoters of Ucp1 and Ppargc1a and recruits positive transcriptional elongation factor b(P-TEFb)to release promoter-proximally paused RNA polymerase II(Pol II),thereby enabling rapid and synchronized transcription of thermogenic genes upon acute cold exposure.Our findings have thus provided a regulatory mechanism of how BAT is prepared to respond to acute cold challenge.
基金This work was supported by grants from the National Natural Science Foundation of China(31988101 and 31730056 to YGC)the National Key Research and Development Program of China(2017YFA0103601 to YGC).
文摘Dear Editor,The intestinal epithelium is a rapidly self-renew-ing tissue for absorbing nutrients and providing bar-rier functions,and its homeostasis is orchestrated by several signaling pathways(Vermeulen and Snip-pert,2014;Zhu et al.,2021).Growing evidence dem-onstrates the importance of cell cycle regulation in intestinal homeostatic maintenance(McKernan and Egan,2015).Here,we report that the E3 ubiquitin ligase adaptor DDB1(Damaged DNA Binding Protein 1)is highly expressed in the intestinal epithelium and regulates the intestinal homeostasis by preventing cell cycle arrest.
文摘利用RNA干涉技术构建水稻DDB1(Damaged DNA binding protein 1)基因不同启动子驱动植物表达载体,DDB1-RNAi和DDB1-glu-RNAi.通过根癌农杆菌介导转入水稻愈伤,经组织培养成功获得转基因植株.半定量RT-PCR分析显示,与野生型植株相比,两组转基因植株幼叶内DDB1的表达量均有不同程度的降低.花粉染色结果显示,转基因植株花粉染色异常,败育率高;植株表现出明显的雄性半不育;秕谷率均有不同程度的提高;并且以上表型在DDB1-RNAi转基因植株中均比在DDB1-glu-RNAi转基因植株中明显.因此,推断DDB1基因与水稻的生殖发育有着密切的关系.
