DHX36 plays a crucial role in regulating transcriptional and post-transcriptional processes through its interaction with G-quadruplexes(G4s).The mechanisms by which DHX36 regulates G4s vary across different cell types...DHX36 plays a crucial role in regulating transcriptional and post-transcriptional processes through its interaction with G-quadruplexes(G4s).The mechanisms by which DHX36 regulates G4s vary across different cell types and physiological conditions.Oocyte-specific conditional knockout(CKO)mice were utilized to study the impact of DHX36 deficiency on female fertility.The results show that the CKO mice exhibit severely impaired hormone response,ovulation,and complete infertility.The CKO germinal vesicle(GV)oocytes display large nucleoli,aberrant chromatin configuration,decreased chromatin accessibility,disturbed transcriptome,and inhibited meiosis progression.Following fertilization,the embryos derived from the CKO oocytes arrest at the zygote or 2-cell stage.Notably,we observed inadequate rRNA transcription in growing GV oocytes,as well as insufficient pre-rRNA processing and translation activity in fully-grown GV oocytes.Using a G4 probe and antibody,we found increased G4s formation at the chromatin and cytoplasm of CKO GV oocytes;these G4s mainly originate from the rDNA and pre-rRNA.Furthermore,the distribution of DHX36 was found to be spatiotemporally synchronized with that of pre-rRNA and G4s in early mouse embryos.In vitro experiments confirmed that DHX36 directly binds with pre-rRNA through the RHAU-specific motif(RSM).Overexpression of DHX36 could partially alleviate the pre-rRNA accumulation in fully-grown CKO oocytes.In conclusion,this study highlights the physiological significance of DHX36 in maintaining female fertility,underscoring its critical role in rRNA homeostasis and chromatin configuration through G4-unwinding mechanism in mouse oocytes.展开更多
Mammalian fertilization begins with the fusion of two specialized gametes,followed by major epigenetic remodeling leading to the formation of a totipotent embryo.During the development of the pre-implantation embryo,p...Mammalian fertilization begins with the fusion of two specialized gametes,followed by major epigenetic remodeling leading to the formation of a totipotent embryo.During the development of the pre-implantation embryo,precise reprogramming progress is a prerequisite for avoiding developmental defects or embryonic lethality,but the underlying molecular mechanisms remain elusive.For the past few years,unprecedented breakthroughs have been made in mapping the regulatory network of dynamic epigenomes during mammalian early embryo development,taking advantage of multiple advances and innovations in low-input genome-wide chromatin analysis technologies.The aim of this review is to highlight the most recent progress in understanding the mechanisms of epigenetic remodeling during early embryogenesis in mammals,including DNA methylation,histone modifications,chromatin accessibility and 3D chromatin organization.展开更多
DNA methylation and histone modification are two of the most characterized epigenetic modifications.With advanced detecting techniques,particularly single-cell sequencing,we can dissect epigenomic patterns and their r...DNA methylation and histone modification are two of the most characterized epigenetic modifications.With advanced detecting techniques,particularly single-cell sequencing,we can dissect epigenomic patterns and their regulatory roles in the growth and differentiation of gametes and early embryos in animals and humans.Assisted reproductive technology(ART)procedures have been shown to influence the methylation of certain genes.Aberrant epigenetic regulation may cause several developmental disorders and clinical diseases.Here,we describe some concepts in epigenetics and review recent researches on DNA methylation and the histone modification profile and their regulatory roles during early embryo development.We also summarize the recent progress in understanding the imprinting disorders associated with ART procedures.展开更多
基金supported by the National Key Research and Development Program of China(2021YFC2700100)the National Natural Science Foundation of China(31930031 and 32300714)+2 种基金the Key Research and Development Program of Zhejiang Province,China(2021C03100 and 2021C03098)the Natural Science Foundation of Zhejiang Province,China(LD22C060001)the National Ten Thousand Talent Program,China.
文摘DHX36 plays a crucial role in regulating transcriptional and post-transcriptional processes through its interaction with G-quadruplexes(G4s).The mechanisms by which DHX36 regulates G4s vary across different cell types and physiological conditions.Oocyte-specific conditional knockout(CKO)mice were utilized to study the impact of DHX36 deficiency on female fertility.The results show that the CKO mice exhibit severely impaired hormone response,ovulation,and complete infertility.The CKO germinal vesicle(GV)oocytes display large nucleoli,aberrant chromatin configuration,decreased chromatin accessibility,disturbed transcriptome,and inhibited meiosis progression.Following fertilization,the embryos derived from the CKO oocytes arrest at the zygote or 2-cell stage.Notably,we observed inadequate rRNA transcription in growing GV oocytes,as well as insufficient pre-rRNA processing and translation activity in fully-grown GV oocytes.Using a G4 probe and antibody,we found increased G4s formation at the chromatin and cytoplasm of CKO GV oocytes;these G4s mainly originate from the rDNA and pre-rRNA.Furthermore,the distribution of DHX36 was found to be spatiotemporally synchronized with that of pre-rRNA and G4s in early mouse embryos.In vitro experiments confirmed that DHX36 directly binds with pre-rRNA through the RHAU-specific motif(RSM).Overexpression of DHX36 could partially alleviate the pre-rRNA accumulation in fully-grown CKO oocytes.In conclusion,this study highlights the physiological significance of DHX36 in maintaining female fertility,underscoring its critical role in rRNA homeostasis and chromatin configuration through G4-unwinding mechanism in mouse oocytes.
基金This work was supported by the National Key R&D Program of China(2016YFA0100400 and 2018YFC1004000)and the National Natural Science Foundation of China(31721003,31820103009,31701262,81630035).
文摘Mammalian fertilization begins with the fusion of two specialized gametes,followed by major epigenetic remodeling leading to the formation of a totipotent embryo.During the development of the pre-implantation embryo,precise reprogramming progress is a prerequisite for avoiding developmental defects or embryonic lethality,but the underlying molecular mechanisms remain elusive.For the past few years,unprecedented breakthroughs have been made in mapping the regulatory network of dynamic epigenomes during mammalian early embryo development,taking advantage of multiple advances and innovations in low-input genome-wide chromatin analysis technologies.The aim of this review is to highlight the most recent progress in understanding the mechanisms of epigenetic remodeling during early embryogenesis in mammals,including DNA methylation,histone modifications,chromatin accessibility and 3D chromatin organization.
基金supported by the National High Technology Research and Development Program(grant number 2015AA020407)the National Natural Science Foundation of China(grant numbers 81521002 and 31522034).
文摘DNA methylation and histone modification are two of the most characterized epigenetic modifications.With advanced detecting techniques,particularly single-cell sequencing,we can dissect epigenomic patterns and their regulatory roles in the growth and differentiation of gametes and early embryos in animals and humans.Assisted reproductive technology(ART)procedures have been shown to influence the methylation of certain genes.Aberrant epigenetic regulation may cause several developmental disorders and clinical diseases.Here,we describe some concepts in epigenetics and review recent researches on DNA methylation and the histone modification profile and their regulatory roles during early embryo development.We also summarize the recent progress in understanding the imprinting disorders associated with ART procedures.
