scholarly journals The H3.3 chaperone Hira complex orchestrates oocyte developmental competence

2020 ◽  
Author(s):  
Rowena Smith ◽  
Zongliang Jiang ◽  
Andrej Susor ◽  
Hao Ming ◽  
Janet Tait ◽  
...  
Keyword(s):  
Chromatin Condensation ◽  
Chromatin Accessibility ◽  
Early Embryo ◽  
Early Embryogenesis ◽  
Developmental Competence ◽  
Specific Gene ◽  
Loss Of Function ◽  
Oocyte Developmental Competence ◽  
Zygote Genome Activation ◽  
Genome Activation

AbstractReproductive success relies on a healthy oocyte competent for fertilisation and capable of sustaining early embryo development. By the end of oogenesis, the oocyte is characterised by a transcriptionally silenced state, but the significance of this state and how it is achieved remains poorly understood. Histone H3.3, one of the H3 variants, has unique functions in chromatin structure and gene expression that are cell cycle-independent. We report here a comprehensive characterisation of the roles of the subunits of the Hira complex (i.e. Hira, Cabin1 and Ubn1), which is primarily responsible for H3.3 deposition during mouse oocyte development. Loss-of-function of any component of the Hira complex led to early embryogenesis failure. Transcriptome and nascent RNA analyses revealed that mutant oocytes fail to silence global transcription. Hira complex mutants are unable to establish the H3K4me3 and H3K9me3 repressive marks, resulting in aberrant chromatin accessibility. Among the misregulated genes in mutant oocytes is Zscan4, a 2-cell specific gene that is involved in zygote genome activation. Overexpression of Zscan4 recapitulates the phenotypes of Hira mutants, illustrating that temporal and spatial expression of Zscan4 is fine-tuned at the oocyte-to-embryo transition. Thus, the H3.3 chaperone Hira complex has a maternal effect function in oocyte developmental competence and early embryogenesis by modulating chromatin condensation and transcriptional quiescence.

scholarly journals Beta-Oxidation Is Essential for Mouse Oocyte Developmental Competence and Early Embryo Development1

2010 ◽  
Vol 83 (6) ◽  
pp. 909-918 ◽  
Author(s):  
Kylie R. Dunning ◽  
Kara Cashman ◽  
Darryl L. Russell ◽  
Jeremy G. Thompson ◽  
Robert J. Norman ◽  
...  
Keyword(s):  
Early Embryo ◽  
Mouse Oocyte ◽  
Developmental Competence ◽  
Beta Oxidation ◽  
Oocyte Developmental Competence

scholarly journals NCAPG Dynamically Coordinates the Myogenesis of Fetal Bovine Tissue by Adjusting Chromatin Accessibility

2020 ◽  
Vol 21 (4) ◽  
pp. 1248
Author(s):  
Xin Hu ◽  
Yishen Xing ◽  
Xing Fu ◽  
Qiyuan Yang ◽  
Ling Ren ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Throughput Sequencing ◽  
Myogenic Differentiation ◽  
Chromatin Condensation ◽  
Chromatin Accessibility ◽  
Myoblast Differentiation ◽  
Specific Gene ◽  
Specific Gene Expression ◽  
Bovine Tissue ◽  
Fetal Bovine

NCAPG is a subunit of condensin I that plays a crucial role in chromatin condensation during mitosis. NCAPG has been demonstrated to be associated with farm animal growth traits. However, its role in regulating myoblast differentiation is still unclear. We used myoblasts derived from fetal bovine tissue as an in vitro model and found that NCAPG was expressed during myogenic differentiation in the cytoplasm and nucleus. Silencing NCAPG prolonged the mitosis and impaired the differentiation due to increased myoblast apoptosis. After 1.5 days of differentiation, silencing NCAPG enhanced muscle-specific gene expression. An assay for transposase-accessible chromatin- high throughput sequencing (ATAC-seq) revealed that silencing NCAPG altered chromatin accessibility to activating protein 1 (AP-1) and its subunits. Knocking down the expression of the AP-1 subunits fos-related antigen 2 (FOSL2) or junB proto-oncogene (JUNB) enhanced part of the muscle-specific gene expression. In conclusion, our data provide valuable evidence about NCAPG’s function in myogenesis, as well as its potential role in gene expression.

scholarly journals Sex-specific transcript diversity is regulated by a maternal pioneer factor in early Drosophila embryos

2021 ◽  
Author(s):  
Mukulika Ray ◽  
Ashley Mae Conard ◽  
Jennifer Urban ◽  
Erica Larschan
Keyword(s):  
Chromatin Accessibility ◽  
Early Embryo ◽  
Specific Transcript ◽  
Genome Wide ◽  
Zygotic Transcription ◽  
Pioneer Factor ◽  
Alternatively Spliced ◽  
Transcript Diversity ◽  
Changes Over Time ◽  
Genome Activation

Maternally deposited RNAs and proteins play a crucial role in initiating zygotic transcription during early embryonic development. However, the mechanisms by which maternal factors regulate zygotic transcript diversity early in development remain poorly understood. Furthermore, how early in development sex-specific transcript diversity occurs is not known genome-wide in any organism. Here, we determine that sex-specific transcript diversity occurs much earlier in development than previously thought in Drosophila, concurrent with Zygotic genome activation (ZGA). We use genetic, biochemical, and genomic approaches to demonstrate that the essential maternally-deposited pioneer factor CLAMP (Chromatin linked adapter for MSL proteins) is a key regulator of sex-specific transcript diversity in the early embryo via the following mechanisms: 1) In both sexes, CLAMP directly binds to the gene bodies of female and male sex-specifically spliced genes. 2) In females, CLAMP modulates chromatin accessibility of an alternatively-spliced exon within Sex-lethal, the master regulator of sex determination, to promote protein production. 3) In males, CLAMP regulates Maleless (MLE) distribution, a spliceosome component to prevent aberrant sex-specific splicing. Thus, we demonstrate for the first time how a maternal factor regulates early zygotic transcriptome diversity sex-specifically. We also developed a new tool to measure how splicing changes over time called time2splice.

scholarly journals DPPA2 and DPPA4 are necessary to establish a totipotent state in mouse embryonic stem cells

2018 ◽  
Author(s):  
Alberto De Iaco ◽  
Alexandre Coudray ◽  
Julien Duc ◽  
Didier Trono
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Chromatin Accessibility ◽  
Early Embryo ◽  
Zygotic Genome Activation ◽  
Cell Stage ◽  
Oocyte Expression ◽  
Genome Activation ◽  
Zygotic Genome

AbstractAfter fertilization of the transcriptionally silent oocyte, expression from both parental chromosomes is launched through so-called zygotic genome activation (ZGA), occurring in the mouse at the 2-cell stage. Amongst the first elements to be transcribed are the Dux gene, the product of which secondarily induces a wide array of ZGA genes, and a subset of evolutionary recent LINE-1 retrotransposons, which regulate chromatin accessibility in the early embryo. The maternally-inherited factors that activate Dux and LINE-1 transcription have so far remained unknown. Here we identify the paralog proteins DPPA2 and DPPA4 as responsible for this process.

scholarly journals Synergistic activity of Nanog, Pou5f3, and Sox19b establishes chromatin accessibility and developmental competence in a context-dependent manner

2020 ◽  
Author(s):  
Liyun Miao ◽  
Yin Tang ◽  
Ashley R. Bonneau ◽  
Shun Hang Chan ◽  
Mina L. Kojima ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Chromatin Accessibility ◽  
Developmental Competence ◽  
Synergistic Activity ◽  
Large Network ◽  
Dependent Manner ◽  
Motif Analysis ◽  
Triple Mutant ◽  
Context Dependent ◽  
Genome Activation

Genome-wide chromatin reprogramming is a fundamental requirement for establishing developmental competence in the newly-formed zygote. In zebrafish, Nanog, Pou5f3 and Sox19b play partially redundant roles in zygotic genome activation, however their interplay in establishing chromatin competency, the context in which they do so and their mechanism of action remain poorly defined. Here, we generated a triple maternal-zygotic nanog-/-;pou5f3-/-;sox19b-/- mutant and assessed the causal relationship between transcription factor (TF) occupancy, chromatin accessibility and genome activation. Analyses of this triple mutant and combinatorial rescues revealed highly synergistic and context-dependent activity of Nanog, Pou5f3, and Sox19b (NPS) in establishing chromatin competency at >50% of active enhancers. Motif analysis revealed a network of TFs that depend on NPS for establishing chromatin accessibility, including the endodermal determinant Eomesa, whose binding we show is regulated by NPS pioneer-like activity. Finally, we demonstrated that NPS play an essential role in establishing H3K27ac and H3K18ac at enhancers and promoters, and that their function in transcriptional activation can be bypassed by targeted recruitment of histone acetyltransferases to individual genes. Altogether, our findings reveal a large network of TFs that function to establish developmental competency, many of which depend on the synergistic and highly context-dependent role of NPS in establishing chromatin accessibility and regulating histone acetylation in order to activate the genome.

scholarly journals The regulatory genome of the malaria vector Anopheles gambiae: integrating chromatin accessibility and gene expression

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
José L Ruiz ◽  
Lisa C Ranford-Cartwright ◽  
Elena Gómez-Díaz
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Anopheles Gambiae ◽  
Mosquito Control ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Malaria Vectors ◽  
Specific Gene ◽  
Mosquito Vector ◽  
Human Malaria

Abstract Anopheles gambiae mosquitoes are primary human malaria vectors, but we know very little about their mechanisms of transcriptional regulation. We profiled chromatin accessibility by the assay for transposase-accessible chromatin by sequencing (ATAC-seq) in laboratory-reared A. gambiae mosquitoes experimentally infected with the human malaria parasite Plasmodium falciparum. By integrating ATAC-seq, RNA-seq and ChIP-seq data, we showed a positive correlation between accessibility at promoters and introns, gene expression and active histone marks. By comparing expression and chromatin structure patterns in different tissues, we were able to infer cis-regulatory elements controlling tissue-specific gene expression and to predict the in vivo binding sites of relevant transcription factors. The ATAC-seq assay also allowed the precise mapping of active regulatory regions, including novel transcription start sites and enhancers that were annotated to mosquito immune-related genes. Not only is this study important for advancing our understanding of mechanisms of transcriptional regulation in the mosquito vector of human malaria, but the information we produced also has great potential for developing new mosquito-control and anti-malaria strategies.

scholarly journals Single cell RNA-seq reveals genes vital to in vitro fertilized embryos and parthenotes in pigs

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhi-Qiang Du ◽  
Hao Liang ◽  
Xiao-Man Liu ◽  
Yun-Hua Liu ◽  
Chonglong Wang ◽  
...  
Keyword(s):  
Embryo Development ◽  
Gene Networks ◽  
Regulatory Networks ◽  
Rna Binding ◽  
Expression Patterns ◽  
Early Embryo ◽  
Specific Factor ◽  
Early Embryos ◽  
Genome Activation

AbstractSuccessful early embryo development requires the correct reprogramming and configuration of gene networks by the timely and faithful execution of zygotic genome activation (ZGA). However, the regulatory principle of molecular elements and circuits fundamental to embryo development remains largely obscure. Here, we profiled the transcriptomes of single zygotes and blastomeres, obtained from in vitro fertilized (IVF) or parthenogenetically activated (PA) porcine early embryos (1- to 8-cell), focusing on the gene expression dynamics and regulatory networks associated with maternal-to-zygote transition (MZT) (mainly maternal RNA clearance and ZGA). We found that minor and major ZGAs occur at 1-cell and 4-cell stages for both IVF and PA embryos, respectively. Maternal RNAs gradually decay from 1- to 8-cell embryos. Top abundantly expressed genes (CDV3, PCNA, CDR1, YWHAE, DNMT1, IGF2BP3, ARMC1, BTG4, UHRF2 and gametocyte-specific factor 1-like) in both IVF and PA early embryos identified are of vital roles for embryo development. Differentially expressed genes within IVF groups are different from that within PA groups, indicating bi-parental and maternal-only embryos have specific sets of mRNAs distinctly decayed and activated. Pathways enriched from DEGs showed that RNA associated pathways (RNA binding, processing, transport and degradation) could be important. Moreover, mitochondrial RNAs are found to be actively transcribed, showing dynamic expression patterns, and for DNA/H3K4 methylation and transcription factors as well. Taken together, our findings provide an important resource to investigate further the epigenetic and genome regulation of MZT events in early embryos of pigs.

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