N^(6)-methyladenosine(m^(6)A)on chromosome-associated regulatory RNAs(carRNAs),including repeat RNAs,plays important roles in tuning the chromatin state and transcription,but the intrinsic mechanism remains unclear.He...N^(6)-methyladenosine(m^(6)A)on chromosome-associated regulatory RNAs(carRNAs),including repeat RNAs,plays important roles in tuning the chromatin state and transcription,but the intrinsic mechanism remains unclear.Here,we report that YTHDC1 plays indispensable roles in the self-renewal and differentiation potency of mouse embryonic stem cells(ESCs),which highly depends on the m^(6)A-binding ability.Ythdcl is required for sufficient rRNA synthesis and repression of the 2-cell(2C)transcriptional program in ESCs,which recapitulates the transcriptome regulation by the LINE1 scaffold.Detailed analyses revealed that YTHDC1 recognizes m^(6)A on LINE1 RNAs in the nucleus and regulates the formation of the LINE1-NCL partnership and the chromatin recruitment of KAP1.Moreover,the establishment of H3K9me3 on 2C-related retrotrans-posons is interrupted in Ythdcl-depleted ESCs and inner cell mass(ICM)cells,which consequently increases the transcriptional activities.Our study reveals a role of m^(6)A in regulating the RNA scaffold,providing a new model for the RNA-chromatin cross-talk.展开更多
It is known that evolutionarily new genes can rapidly evolve essential roles in fundamental biological processes. Nevertheless, the underlying molecular mechanism of how they acquire theft novel transcriptional patter...It is known that evolutionarily new genes can rapidly evolve essential roles in fundamental biological processes. Nevertheless, the underlying molecular mechanism of how they acquire theft novel transcriptional pattern is less characterized except for the role ofcis-regulatory evolution. Epigenetic modification offers an alternative possibility. Here, we examined how histone modifications have changed among different gene age groups in Drosophila melanogaster by integrative analyses of an updated new gene dataset and published epigenomic data. We found a robust pattern across various datasets where both the coverage and intensity of active histone modifications, histone 3 lysine 4 trimethylation and lysine 36 trimethylation, increased with evolutionary age. Such a temporal correlation is negative and much weaker for the repressive histone mark, lysine 9 trimethylation, which is expected given its major association with heterochromatin. By further comparison with neighboring old genes, the depletion of active marks of new genes could be only partially explained by the local epigenetic context. All these data are consistent with the observation that older genes bear relatively higher expression levels and suggest that the evolution of histone modifications could be implicated in transcriptional evolution after gene birth.展开更多
基金This work was supported by the National Key R&D Program of China(2016YFA0100400,2020YFA0113200,2018YFA0108900 and 2016YFC1000600)the National Natural Science Foundation of China(31922022,31771646,82022027,31721003,31970796,31871448 and 31871446)+3 种基金the Shanghai Rising-Star Program(19QA1409600)the Shanghai Municipal Medical and Health Discipline Construction Projects(2017ZZ02015)the Fundamental Research Funds for the Central Universities(1515219049 and 22120200410)the Major Program of the Development Fund for Shanghai Zhangjiang National Innovation Demonstration Zone(ZJ2018-ZD-004).
文摘N^(6)-methyladenosine(m^(6)A)on chromosome-associated regulatory RNAs(carRNAs),including repeat RNAs,plays important roles in tuning the chromatin state and transcription,but the intrinsic mechanism remains unclear.Here,we report that YTHDC1 plays indispensable roles in the self-renewal and differentiation potency of mouse embryonic stem cells(ESCs),which highly depends on the m^(6)A-binding ability.Ythdcl is required for sufficient rRNA synthesis and repression of the 2-cell(2C)transcriptional program in ESCs,which recapitulates the transcriptome regulation by the LINE1 scaffold.Detailed analyses revealed that YTHDC1 recognizes m^(6)A on LINE1 RNAs in the nucleus and regulates the formation of the LINE1-NCL partnership and the chromatin recruitment of KAP1.Moreover,the establishment of H3K9me3 on 2C-related retrotrans-posons is interrupted in Ythdcl-depleted ESCs and inner cell mass(ICM)cells,which consequently increases the transcriptional activities.Our study reveals a role of m^(6)A in regulating the RNA scaffold,providing a new model for the RNA-chromatin cross-talk.
文摘It is known that evolutionarily new genes can rapidly evolve essential roles in fundamental biological processes. Nevertheless, the underlying molecular mechanism of how they acquire theft novel transcriptional pattern is less characterized except for the role ofcis-regulatory evolution. Epigenetic modification offers an alternative possibility. Here, we examined how histone modifications have changed among different gene age groups in Drosophila melanogaster by integrative analyses of an updated new gene dataset and published epigenomic data. We found a robust pattern across various datasets where both the coverage and intensity of active histone modifications, histone 3 lysine 4 trimethylation and lysine 36 trimethylation, increased with evolutionary age. Such a temporal correlation is negative and much weaker for the repressive histone mark, lysine 9 trimethylation, which is expected given its major association with heterochromatin. By further comparison with neighboring old genes, the depletion of active marks of new genes could be only partially explained by the local epigenetic context. All these data are consistent with the observation that older genes bear relatively higher expression levels and suggest that the evolution of histone modifications could be implicated in transcriptional evolution after gene birth.
