Osteoclast is critical in skeletal development and fracture healing,yet the impact and underlying mechanisms of their metabolic state on these processes remain unclear.Here,by using osteoclast-specific small GTPase Rh...Osteoclast is critical in skeletal development and fracture healing,yet the impact and underlying mechanisms of their metabolic state on these processes remain unclear.Here,by using osteoclast-specific small GTPase Rheb1-knockout mice,we reveal that mitochondrial respiration,rather than glycolysis,is essential for cathepsin K(CTSK)production in osteoclasts and is regulated by Rheb1 in a mechanistic target of rapamycin complex 1(mTORC1)-independent manner.展开更多
Dear Editor, In mammalian genomes, pervasive transcription produces thousands of long non-coding RNA （IncRNA） transcripts （Olebali et al., 2012; Hon et al., 2017）. Compared to protein-coding mRNAs, IncRNAs are le...Dear Editor, In mammalian genomes, pervasive transcription produces thousands of long non-coding RNA （IncRNA） transcripts （Olebali et al., 2012; Hon et al., 2017）. Compared to protein-coding mRNAs, IncRNAs are less conserved, and often exhibit low-level, developmental stage-and tissue-specific expression （Pauli et al., 2011; Hu et al., 2012; Lee, 2012; Ulitsky and Bartel, 2013; Cech and Steitz, 2014; Hon et al., 2017）. Many IncRNAs are strongly correlated with their neighboring mRNA genes in terms of expression and function, and tend to regulate nearby transcription （Orom et al., 2010; Engreitz et al., 2016; Luo etal., 2016）. It has been implicated that IncRNAs play versatile roles in regulating diverse aspects of cell biology through mechanisms at multiple levels （Pauli et al., 2011; Lee.展开更多
The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions.However,the molecular machinery underlying these hierarchically organized three-dim...The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions.However,the molecular machinery underlying these hierarchically organized three-dimensional(3D)chromatin architecture and dynamics remains poorly understood.Here by combining imaging and sequencing,we studied the role of lamin B1 in chromatin architecture and dynamics.We found that lamin B1 depletion leads to detachment of lamina-associated domains(LADs)from the nuclear periphery accompanied with global chromatin redistribution and decompaction.Consequently,the interchromosomal as well as inter-compartment interactions are increased,but the structure of topologically associating domains(TADs)is not affected.Using live-cell genomic loci tracking,we further proved that depletion of lamin B1 leads to increased chromatin dynamics,owing to chromatin decompaction and redistribution toward nucleoplasm.Taken together,our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance,chromatin compaction,genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics,supporting their crucial roles in chromatin higher-order structure and chromatin dynamics.展开更多
基金supported by Grant Nos.31872799,82070906 and 31701033 from the National Natural Science Foundation of ChinaGrant Nos.2020A1515011189 from Guangdong Basic and Applied Basic Research Foundation of China。
文摘Osteoclast is critical in skeletal development and fracture healing,yet the impact and underlying mechanisms of their metabolic state on these processes remain unclear.Here,by using osteoclast-specific small GTPase Rheb1-knockout mice,we reveal that mitochondrial respiration,rather than glycolysis,is essential for cathepsin K(CTSK)production in osteoclasts and is regulated by Rheb1 in a mechanistic target of rapamycin complex 1(mTORC1)-independent manner.
文摘Dear Editor, In mammalian genomes, pervasive transcription produces thousands of long non-coding RNA （IncRNA） transcripts （Olebali et al., 2012; Hon et al., 2017）. Compared to protein-coding mRNAs, IncRNAs are less conserved, and often exhibit low-level, developmental stage-and tissue-specific expression （Pauli et al., 2011; Hu et al., 2012; Lee, 2012; Ulitsky and Bartel, 2013; Cech and Steitz, 2014; Hon et al., 2017）. Many IncRNAs are strongly correlated with their neighboring mRNA genes in terms of expression and function, and tend to regulate nearby transcription （Orom et al., 2010; Engreitz et al., 2016; Luo etal., 2016）. It has been implicated that IncRNAs play versatile roles in regulating diverse aspects of cell biology through mechanisms at multiple levels （Pauli et al., 2011; Lee.
基金This work is supported by grants from National Key R&D Program of China,No.2017YFA0505302the National Science Foundation of China 21573013,21825401 for Y.S.+1 种基金Chinese National Key Projects of Research and Development,No.2016YFA0100103,Peking-Tsinghua Center for Life SciencesNational Natural Science Foundation of China Key Research Grant 31871266 for C.L。
文摘The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions.However,the molecular machinery underlying these hierarchically organized three-dimensional(3D)chromatin architecture and dynamics remains poorly understood.Here by combining imaging and sequencing,we studied the role of lamin B1 in chromatin architecture and dynamics.We found that lamin B1 depletion leads to detachment of lamina-associated domains(LADs)from the nuclear periphery accompanied with global chromatin redistribution and decompaction.Consequently,the interchromosomal as well as inter-compartment interactions are increased,but the structure of topologically associating domains(TADs)is not affected.Using live-cell genomic loci tracking,we further proved that depletion of lamin B1 leads to increased chromatin dynamics,owing to chromatin decompaction and redistribution toward nucleoplasm.Taken together,our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance,chromatin compaction,genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics,supporting their crucial roles in chromatin higher-order structure and chromatin dynamics.
