赖氨酸特异性去甲基化酶6B(lysine-specific demethylase 6B,KDM6B)是含Jumonji C结构域蛋白家族(Jumonji C domain-containing protein family,JmjC)中的一种重要表观遗传因子,不仅在细胞分化、炎症反应、组织稳态和神经性疾病中发挥...赖氨酸特异性去甲基化酶6B(lysine-specific demethylase 6B,KDM6B)是含Jumonji C结构域蛋白家族(Jumonji C domain-containing protein family,JmjC)中的一种重要表观遗传因子,不仅在细胞分化、炎症反应、组织稳态和神经性疾病中发挥表观遗传调控作用,还对巨噬细胞的功能、免疫反应等具有关键调控意义。作为JmjC家族中唯一能响应类Toll受体(Toll-like receptor,TLR)信号的成员,KDM6B可在TLR信号刺激下被激活从而发挥功能。研究发现,KDM6B可以通过调节巨噬细胞的极化、影响细胞因子的表达水平以及参与肿瘤微环境调控等方式影响巨噬细胞,因此,KDM6B在免疫反应、炎症反应以及肿瘤等病理生理过程中发挥重要作用。KDM6B作为关键的表观遗传因子对巨噬细胞的功能具有调控作用,包括调节巨噬细胞的极化、炎症反应以及促纤维化等,有望成为研究免疫、炎症及肿瘤等相关疾病的潜在靶点。展开更多
In the mammalian genome,most CpGs are methylated.However,CpGs within the CpG islands(CGIs)are largely unmethylated,which are important for gene expression regulation.The mechanism underlying the low methylation levels...In the mammalian genome,most CpGs are methylated.However,CpGs within the CpG islands(CGIs)are largely unmethylated,which are important for gene expression regulation.The mechanism underlying the low methylation levels at CGIs remains largely elusive.KDM2 proteins(KDM2A and KDM2B)are H3K36me2 demethylases known to bind specifically at CGIs.Here,we report that depletion of each or both KDM2 proteins,or mutation of all their JmjC domains that harbor the H3K36me2 demethylation activity,leads to an increase in DNA methylation at selective CGIs.The Kdm2a/2b double knockout shows a stronger increase in DNA methylation compared with the single mutant of Kdm2a or Kdm2b,indicating that KDM2A and KDM2B redundantly regulate DNA methylation at CGIs.In addition,the increase of CGI DNA methylation upon mutations of KDM2 proteins is associated with the chromatin environment.Our findings reveal that KDM2A and KDM2B function redundantly in regulating DNA methylation at a subset of CGIs in an H3K36me2 demethylation-dependent manner.展开更多
Tissue interactions play a crucial role in tooth development.Notably,extracellular vesicle-mediated interactions between the mandible and tooth germ are considered essential.Here,we revealed that mandible extracellula...Tissue interactions play a crucial role in tooth development.Notably,extracellular vesicle-mediated interactions between the mandible and tooth germ are considered essential.Here,we revealed that mandible extracellular vesicles could modulate the proliferation and differentiation of dental mesenchymal cells by regulating the histone demethylase KDM2B.Further investigation showed that mandible derived extracellular vesicles could deliver miR-206 to KDM2B,thereby regulating tooth development.An animal study demonstrated that the miR-206/KDM2B pathway affected tooth morphogenesis and mineralization after eight weeks of subcutaneous transplantation in nude mice.In conclusion,this study suggested that the mandible played a critical role in tooth morphogenesis and mineralization,which could be a potential therapeutic target for abnormal tooth development and an alternative model for tooth regeneration.展开更多
文摘赖氨酸特异性去甲基化酶6B(lysine-specific demethylase 6B,KDM6B)是含Jumonji C结构域蛋白家族(Jumonji C domain-containing protein family,JmjC)中的一种重要表观遗传因子,不仅在细胞分化、炎症反应、组织稳态和神经性疾病中发挥表观遗传调控作用,还对巨噬细胞的功能、免疫反应等具有关键调控意义。作为JmjC家族中唯一能响应类Toll受体(Toll-like receptor,TLR)信号的成员,KDM6B可在TLR信号刺激下被激活从而发挥功能。研究发现,KDM6B可以通过调节巨噬细胞的极化、影响细胞因子的表达水平以及参与肿瘤微环境调控等方式影响巨噬细胞,因此,KDM6B在免疫反应、炎症反应以及肿瘤等病理生理过程中发挥重要作用。KDM6B作为关键的表观遗传因子对巨噬细胞的功能具有调控作用,包括调节巨噬细胞的极化、炎症反应以及促纤维化等,有望成为研究免疫、炎症及肿瘤等相关疾病的潜在靶点。
基金supported by the National Natural Science Foundation of China(32070607)the National Key Research and Development Program of China(2020YFA0804000)the CAS Project for Young Scientists in Basic Research(YSBR-012).
文摘In the mammalian genome,most CpGs are methylated.However,CpGs within the CpG islands(CGIs)are largely unmethylated,which are important for gene expression regulation.The mechanism underlying the low methylation levels at CGIs remains largely elusive.KDM2 proteins(KDM2A and KDM2B)are H3K36me2 demethylases known to bind specifically at CGIs.Here,we report that depletion of each or both KDM2 proteins,or mutation of all their JmjC domains that harbor the H3K36me2 demethylation activity,leads to an increase in DNA methylation at selective CGIs.The Kdm2a/2b double knockout shows a stronger increase in DNA methylation compared with the single mutant of Kdm2a or Kdm2b,indicating that KDM2A and KDM2B redundantly regulate DNA methylation at CGIs.In addition,the increase of CGI DNA methylation upon mutations of KDM2 proteins is associated with the chromatin environment.Our findings reveal that KDM2A and KDM2B function redundantly in regulating DNA methylation at a subset of CGIs in an H3K36me2 demethylation-dependent manner.
基金supported by the National Natural Science Foundation of China(No.82071078,82370939)the Shaanxi Provincial High-level Talent Program and Young Talent Support Plan of Xi’an Jiaotong University.
文摘Tissue interactions play a crucial role in tooth development.Notably,extracellular vesicle-mediated interactions between the mandible and tooth germ are considered essential.Here,we revealed that mandible extracellular vesicles could modulate the proliferation and differentiation of dental mesenchymal cells by regulating the histone demethylase KDM2B.Further investigation showed that mandible derived extracellular vesicles could deliver miR-206 to KDM2B,thereby regulating tooth development.An animal study demonstrated that the miR-206/KDM2B pathway affected tooth morphogenesis and mineralization after eight weeks of subcutaneous transplantation in nude mice.In conclusion,this study suggested that the mandible played a critical role in tooth morphogenesis and mineralization,which could be a potential therapeutic target for abnormal tooth development and an alternative model for tooth regeneration.
