Once thought to be transcriptional noise, large non-coding RNAs （IncRNAs） have recently been demonstrated to be functional molecules. The cell-type-specific expression patterns of lncRNAs suggest that their transcri...Once thought to be transcriptional noise, large non-coding RNAs （IncRNAs） have recently been demonstrated to be functional molecules. The cell-type-specific expression patterns of lncRNAs suggest that their transcription may be regulated epigenetically. Using a custom-designed microarray, here we examine the expression profile of IncRNAs in embryonic stem （ES） cells, lineage-restricted neuronal progenitor cells, and terminally differentiated fibroblasts. In addition, we also analyze the relationship between their expression and their promoter H3K4 and H3K27 methyla- tion patterns. We find that numerous lncRNAs in these cell types undergo changes in the levels of expression and promoter H3K4me3 and H3K27me3. Interestingly, lncRNAs that are expressed at lower levels in ES cells exhibit higher levels of H3K27me3 at their promoters. Consistent with this result, knockdown of the H3K27me3 methyltransferase Ezh2 results in derepression of these IncRNAs in ES cells. Thus, our results establish a role for Ezh2-mediated H3K27 methylation in lncRNA silencing in ES cells and reveal that lncRNAs are subject to epigenetic regulation in a similar manner to that of the protein-coding genes.展开更多
Although Activin/Nodal signaling regulates pluripotency of human embryonic stem （ES） cells, how this signaling acts in mouse ES cells remains largely unclear. To investigate this, we confirmed that mouse ES cells po...Although Activin/Nodal signaling regulates pluripotency of human embryonic stem （ES） cells, how this signaling acts in mouse ES cells remains largely unclear. To investigate this, we confirmed that mouse ES cells possess active Smad2-mediated Activin/Nodal signaling and found that Smad2-mediated Activin/Nodal signaling is dispensable for self-renewal maintenance but is required for proper differentiation toward the mesendoderm lineage. To gain insights into the underlying mechanisms, Smad2-associated genes were identified by genome-wide chromatin immu- noprecipitation-chip analysis. The results showed that there is a transcriptional correlation between Smad2 binding and Activin/Nodal signaling modulation, and that the development-related genes were enriched among the Smad2- bound targets. We further identified Tapbp as a key player in mesendoderm differentiation of mouse ES cells acting downstream of the Activin/Nodal-Smad2 pathway. Taken together, our findings suggest that Smad2-mediated Activin/Nodal signaling orchestrates mesendoderm lineage commitment of mouse ES cells through direct modulation of corresponding developmental regulator expression.展开更多
In present paper, one of the T-DNA insertional embryonic lethal mutant of Arabidopsis is identifled and designated as acd mutant. The embryo development of this mutant is arrested in globular stage. The cell division ...In present paper, one of the T-DNA insertional embryonic lethal mutant of Arabidopsis is identifled and designated as acd mutant. The embryo development of this mutant is arrested in globular stage. The cell division pattern is abnormal during early embryogenesis and results in disturbed cellular differentiation. Most of mutant embryos are finally degenerated and aborted in globular stage. However, a few of them still can germinate in agar plate and produce seedlings with shorter hypocotyl and distorted shoot meristem. To understand the molecular basis of the phenotype of this mutant, the joint fragment of T-DNA/plant DNA is isolated by plasmid rescue and Dig-labeled as probe for cDNA library screening. According to the sequence analysis and similarity searching, a 936bp cDNA sequence (EMBL accession#: Y12555) from selected positive clone shows a 99.8 % (923/925bp) sequence homology with Alanyl-tRNA Synthetase (A1aRS) gene of Arabidopsis thaliana. Furthermore, the data of in sitll hybridization experiment indicate that the expression of AlaRS gene is weak in early embryogenesis and declines along with globular embryo ’development’ in this mutant.Accordingly, the reduced expression of AlaRS gene maybe closely related to the morphological changes in early embryogenesis of this lethal mutant.展开更多
Apolipoprotein C1 （Apocl） is associated with lipoprotein metabolism, but its physiological role during embryogenesis is largely unknown. We reveal a new function of Apoclb, a transcript isoform of Apocl, in epiboly ...Apolipoprotein C1 （Apocl） is associated with lipoprotein metabolism, but its physiological role during embryogenesis is largely unknown. We reveal a new function of Apoclb, a transcript isoform of Apocl, in epiboly during zebrafish gastrulation. Apoclb is expressed in yolk syncytial layers and in deep cells of the ventral and lateral region of the embryos. It displays a ra- dial gradient with high levels in the interior layer and low levels in the superficial layer. Knockdown of Apoclb by injecting antisense morpholino （MO） caused the epiboly arrest in deep cells. Moreover, we show that the radial intercalation and the ra- dial gradient distribution of E-cadherin are disrupted both in Apoclb knockdown and overexpressed embryos. Therefore, Apoc 1 b controls epiboly via E-cadherin-mediated radial intercalation in a gradient-dependent manner.展开更多
Bucky ball(Buc)is involved in germ plasm(GP)assembly during early zebrafish development by regulating GP mRNA expression via an unknown mechanism.The present study demonstrates that an m^(6)A reader Igf2bp3 interacts ...Bucky ball(Buc)is involved in germ plasm(GP)assembly during early zebrafish development by regulating GP mRNA expression via an unknown mechanism.The present study demonstrates that an m^(6)A reader Igf2bp3 interacts and colocalizes with Buc in the GP.Similar to the loss of Buc,the genetic deletion of maternal igf2bp3 in zebrafish leads to abnormal GP assembly and insufficient germ cell specification,which can be partially restored by the injection of igf2 bp3 mRNA.Igf2bp3 binds to m^(6)A-modified GPorganizer and GP mRNAs in an m^(6)A-dependent manner and prevents their degradation.These findings indicate that the functions of Igf2bp3,a direct effector protein of Buc,in GP mRNA expression and GP assembly involve m^(6)A-dependent regulation;these results emphasize a critical role of m^(6)A modification in the process of GP assembly.展开更多
Hematopoietic stem cells (HSCs), which are localized in the bone marrow of adult mammals, come from hematopoietic endothelium during embryonic stages. Although the basic processes of HSC generation and differentiation...Hematopoietic stem cells (HSCs), which are localized in the bone marrow of adult mammals, come from hematopoietic endothelium during embryonic stages. Although the basic processes of HSC generation and differentiation have been described in the past, the epigenetic regulation of embryonic hematopoiesis remains to be fully described. Here, by utilizing an in vitro differentiation system of mouse embryonic stem cells (ESCs), we identified more than 20 microRNAs that were highly enriched in embryonic hematopoietic cells, including some (e.g. miR-10b, miR-15b, and miR-27a) with previously unknown functions in blood formation. Luciferase and gene expression assays further revealed combinational binding and regulation of these microRNAs by key transcription factors in blood cells. Finally, bioinformatics and functional analyses supported an interactive regulatory control between transcription factors and microRNAs in hematopoiesis.展开更多
Mammalian cortical development is a dynamically and strictly regulated process orchestrated by extracellular signals and intracellular mechanisms. Recent studies show that epigenetic regulation serves as, at least in ...Mammalian cortical development is a dynamically and strictly regulated process orchestrated by extracellular signals and intracellular mechanisms. Recent studies show that epigenetic regulation serves as, at least in part, interfaces between genes and the environment, and also provides insight into the molecular and cellular bases of early embryonic cortical development. It is becoming increasingly clear that epigenetic regulation of cortical development occurs at multiple levels and that comprehensive knowledge of this complex regulatory landscape is essential to delineating embryonic neurogenesis.展开更多
文摘Once thought to be transcriptional noise, large non-coding RNAs （IncRNAs） have recently been demonstrated to be functional molecules. The cell-type-specific expression patterns of lncRNAs suggest that their transcription may be regulated epigenetically. Using a custom-designed microarray, here we examine the expression profile of IncRNAs in embryonic stem （ES） cells, lineage-restricted neuronal progenitor cells, and terminally differentiated fibroblasts. In addition, we also analyze the relationship between their expression and their promoter H3K4 and H3K27 methyla- tion patterns. We find that numerous lncRNAs in these cell types undergo changes in the levels of expression and promoter H3K4me3 and H3K27me3. Interestingly, lncRNAs that are expressed at lower levels in ES cells exhibit higher levels of H3K27me3 at their promoters. Consistent with this result, knockdown of the H3K27me3 methyltransferase Ezh2 results in derepression of these IncRNAs in ES cells. Thus, our results establish a role for Ezh2-mediated H3K27 methylation in lncRNA silencing in ES cells and reveal that lncRNAs are subject to epigenetic regulation in a similar manner to that of the protein-coding genes.
基金Acknowledgments We thank Gaoyang Zhu for technical assistance. This work was supported by grants from the National Natural Science Foundation of China （30930050, 30921004）, the 973 Program （2006CB943401, 2010CB833706） to YGC, and grants from the China National Science Foundation （Grant # 30890033, 30588001 and 30620120433）, Chinese Ministry of Science and Technology（Grant # 2006CB910700） to JDH.
文摘Although Activin/Nodal signaling regulates pluripotency of human embryonic stem （ES） cells, how this signaling acts in mouse ES cells remains largely unclear. To investigate this, we confirmed that mouse ES cells possess active Smad2-mediated Activin/Nodal signaling and found that Smad2-mediated Activin/Nodal signaling is dispensable for self-renewal maintenance but is required for proper differentiation toward the mesendoderm lineage. To gain insights into the underlying mechanisms, Smad2-associated genes were identified by genome-wide chromatin immu- noprecipitation-chip analysis. The results showed that there is a transcriptional correlation between Smad2 binding and Activin/Nodal signaling modulation, and that the development-related genes were enriched among the Smad2- bound targets. We further identified Tapbp as a key player in mesendoderm differentiation of mouse ES cells acting downstream of the Activin/Nodal-Smad2 pathway. Taken together, our findings suggest that Smad2-mediated Activin/Nodal signaling orchestrates mesendoderm lineage commitment of mouse ES cells through direct modulation of corresponding developmental regulator expression.
文摘In present paper, one of the T-DNA insertional embryonic lethal mutant of Arabidopsis is identifled and designated as acd mutant. The embryo development of this mutant is arrested in globular stage. The cell division pattern is abnormal during early embryogenesis and results in disturbed cellular differentiation. Most of mutant embryos are finally degenerated and aborted in globular stage. However, a few of them still can germinate in agar plate and produce seedlings with shorter hypocotyl and distorted shoot meristem. To understand the molecular basis of the phenotype of this mutant, the joint fragment of T-DNA/plant DNA is isolated by plasmid rescue and Dig-labeled as probe for cDNA library screening. According to the sequence analysis and similarity searching, a 936bp cDNA sequence (EMBL accession#: Y12555) from selected positive clone shows a 99.8 % (923/925bp) sequence homology with Alanyl-tRNA Synthetase (A1aRS) gene of Arabidopsis thaliana. Furthermore, the data of in sitll hybridization experiment indicate that the expression of AlaRS gene is weak in early embryogenesis and declines along with globular embryo ’development’ in this mutant.Accordingly, the reduced expression of AlaRS gene maybe closely related to the morphological changes in early embryogenesis of this lethal mutant.
基金supported by grants from the National Basic Research Program of China(2010CB126300)the National High Technology Research and Development Program of China(2012AA092201-3)+1 种基金Ministry of Agriculture of China within the special Fund for Agro-scientific Research in the Public Interest(200903045)the National Natural Science Foundation of China(30971414)
文摘Apolipoprotein C1 （Apocl） is associated with lipoprotein metabolism, but its physiological role during embryogenesis is largely unknown. We reveal a new function of Apoclb, a transcript isoform of Apocl, in epiboly during zebrafish gastrulation. Apoclb is expressed in yolk syncytial layers and in deep cells of the ventral and lateral region of the embryos. It displays a ra- dial gradient with high levels in the interior layer and low levels in the superficial layer. Knockdown of Apoclb by injecting antisense morpholino （MO） caused the epiboly arrest in deep cells. Moreover, we show that the radial intercalation and the ra- dial gradient distribution of E-cadherin are disrupted both in Apoclb knockdown and overexpressed embryos. Therefore, Apoc 1 b controls epiboly via E-cadherin-mediated radial intercalation in a gradient-dependent manner.
基金supported by the National Key R&D Program of China(2018YFD0901201 and 2019YFA0802801)China Agricultural Research System(CARS-46)+3 种基金the National Natural Science Foundation of China(31870820)the Innovative Research Group Program of Hubei Province(2020CFA017)the Medical Science Advancement Program of Wuhan University(TFJC2018004)the Fundamental Research Funds for the Central Universities(2042019kf0207)。
文摘Bucky ball(Buc)is involved in germ plasm(GP)assembly during early zebrafish development by regulating GP mRNA expression via an unknown mechanism.The present study demonstrates that an m^(6)A reader Igf2bp3 interacts and colocalizes with Buc in the GP.Similar to the loss of Buc,the genetic deletion of maternal igf2bp3 in zebrafish leads to abnormal GP assembly and insufficient germ cell specification,which can be partially restored by the injection of igf2 bp3 mRNA.Igf2bp3 binds to m^(6)A-modified GPorganizer and GP mRNAs in an m^(6)A-dependent manner and prevents their degradation.These findings indicate that the functions of Igf2bp3,a direct effector protein of Buc,in GP mRNA expression and GP assembly involve m^(6)A-dependent regulation;these results emphasize a critical role of m^(6)A modification in the process of GP assembly.
基金supported by the Ministry of Science and Technology of China(2016YFA0100302, 2014CB964800)the National Natural Science Foundation of China (31471347, 30971522, 31271589)the Science and Technology Commission of Shanghai Municipality (11DZ2260300, 13JC1406402,16JC1404200)
文摘Hematopoietic stem cells (HSCs), which are localized in the bone marrow of adult mammals, come from hematopoietic endothelium during embryonic stages. Although the basic processes of HSC generation and differentiation have been described in the past, the epigenetic regulation of embryonic hematopoiesis remains to be fully described. Here, by utilizing an in vitro differentiation system of mouse embryonic stem cells (ESCs), we identified more than 20 microRNAs that were highly enriched in embryonic hematopoietic cells, including some (e.g. miR-10b, miR-15b, and miR-27a) with previously unknown functions in blood formation. Luciferase and gene expression assays further revealed combinational binding and regulation of these microRNAs by key transcription factors in blood cells. Finally, bioinformatics and functional analyses supported an interactive regulatory control between transcription factors and microRNAs in hematopoiesis.
基金supported by the Chinese Ministry of Science and Technology(2015CB964501 and2014CB964903)the National Natural Science Foundation of China(31371477)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA01020301)
文摘Mammalian cortical development is a dynamically and strictly regulated process orchestrated by extracellular signals and intracellular mechanisms. Recent studies show that epigenetic regulation serves as, at least in part, interfaces between genes and the environment, and also provides insight into the molecular and cellular bases of early embryonic cortical development. It is becoming increasingly clear that epigenetic regulation of cortical development occurs at multiple levels and that comprehensive knowledge of this complex regulatory landscape is essential to delineating embryonic neurogenesis.
