scholarly journals Satb2 acts as a gatekeeper for major developmental transitions during early vertebrate embryogenesis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Saurabh J. Pradhan ◽  
Puli Chandramouli Reddy ◽  
Michael Smutny ◽  
Ankita Sharma ◽  
Keisuke Sako ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Chromatin Accessibility ◽  
Dna Binding Proteins ◽  
Developmental Transitions ◽  
Pluripotency Factors ◽  
Neural Crest Development ◽  
Genome Wide ◽  
Zebrafish Embryogenesis ◽  
Genome Activation ◽  
Zygotic Genome

AbstractZygotic genome activation (ZGA) initiates regionalized transcription underlying distinct cellular identities. ZGA is dependent upon dynamic chromatin architecture sculpted by conserved DNA-binding proteins. However, the direct mechanistic link between the onset of ZGA and the tissue-specific transcription remains unclear. Here, we have addressed the involvement of chromatin organizer Satb2 in orchestrating both processes during zebrafish embryogenesis. Integrative analysis of transcriptome, genome-wide occupancy and chromatin accessibility reveals contrasting molecular activities of maternally deposited and zygotically synthesized Satb2. Maternal Satb2 prevents premature transcription of zygotic genes by influencing the interplay between the pluripotency factors. By contrast, zygotic Satb2 activates transcription of the same group of genes during neural crest development and organogenesis. Thus, our comparative analysis of maternal versus zygotic function of Satb2 underscores how these antithetical activities are temporally coordinated and functionally implemented highlighting the evolutionary implications of the biphasic and bimodal regulation of landmark developmental transitions by a single determinant.

scholarly journals Satb2 acts as a gatekeeper for major developmental transitions during early vertebrate embryogenesis

2020 ◽  
Author(s):  
Saurabh J. Pradhan ◽  
Puli Chandramouli Reddy ◽  
Michael Smutny ◽  
Ankita Sharma ◽  
Keisuke Sako ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Dna Binding ◽  
Chromatin Accessibility ◽  
Dna Binding Proteins ◽  
Developmental Transitions ◽  
Pluripotency Factors ◽  
Neural Crest Development ◽  
Genome Wide ◽  
Genome Activation ◽  
Zygotic Genome

AbstractZygotic genome activation (ZGA) initiates regionalized transcription responsible for the acquisition of distinct cellular identities. ZGA is dependent upon dynamic chromatin architecture sculpted by conserved DNA-binding proteins. However, whether the tissue-specific transcription is mechanistically linked with the onset of ZGA is unknown. Here, we have addressed the involvement of chromatin organizer SATB2 in orchestrating these processes during vertebrate embryogenesis. Integrative analysis of transcriptome, genome-wide occupancy and chromatin accessibility revealed contrasting molecular functions of maternal and zygotic pools of Satb2. Maternal Satb2 represses zygotic genes by influencing the interplay between the pluripotency factors. By contrast, zygotic Satb2 activates transcription of the same group of genes during neural crest development and organogenesis. Comparative analysis of maternal versus zygotic function of Satb2 underscores how these antithetical activities are temporally coordinated and functionally implemented. We discuss the evolutionary implications of the biphasic and bimodal regulation of landmark developmental transitions by a single determinant.

CLAMP regulates Zygotic Genome Activation in Drosophila embryos

Genetics ◽  
2021 ◽  
Author(s):  
Megan M Colonnetta ◽  
Juan E Abrahante ◽  
Paul Schedl ◽  
Daryl M Gohl ◽  
Girish Deshpande
Keyword(s):  
Temporal Dynamics ◽  
Embryonic Patterning ◽  
Zygotic Genome Activation ◽  
Promoter Sequences ◽  
Genome Wide ◽  
Zygotic Transcription ◽  
Pioneer Factor ◽  
Genome Activation ◽  
Drosophila Embryos ◽  
Zygotic Genome

Abstract Embryonic patterning is critically dependent on zygotic genome activation (ZGA). In Drosophila melanogaster embryos, the pioneer factor Zelda directs ZGA, possibly in conjunction with other factors. Here we have explored novel involvement of Chromatin-Linked Adapter for MSL Proteins (CLAMP) during ZGA. CLAMP binds thousands of sites genome-wide throughout early embryogenesis. Interestingly, CLAMP relocates to target promoter sequences across the genome when ZGA is initiated. Although there is a considerable overlap between CLAMP and Zelda binding sites, the proteins display distinct temporal dynamics. To assess whether CLAMP occupancy affects gene expression, we analyzed transcriptomes of embryos zygotically compromised for either clamp or zelda and found that transcript levels of many zygotically-activated genes are similarly affected. Importantly, compromising either clamp or zelda disrupted the expression of critical segmentation and sex determination genes bound by CLAMP (and Zelda). Furthermore, clamp knockdown embryos recapitulate other phenotypes observed in Zelda-depleted embryos, including nuclear division defects, centrosome aberrations, and a disorganized actomyosin network. Based on these data, we propose that CLAMP acts in concert with Zelda to regulate early zygotic transcription.

scholarly journals Pluripotency factors select gene expression repertoire at Zygotic Genome Activation

2020 ◽  
Author(s):  
Meijiang Gao ◽  
Marina Veil ◽  
Marcus Rosenblatt ◽  
Anna Gebhard ◽  
Helge Hass ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Early Gene ◽  
Zebrafish Embryos ◽  
Fate Specification ◽  
Pluripotency Factors ◽  
Zygotic Transcription ◽  
Simultaneous Loss ◽  
Genome Activation ◽  
Zygotic Genome

AbstractAwakening of zygotic transcription in animal embryos relies on maternal pioneer transcription factors. The interplay of global and specific functions of these proteins remains poorly understood. Here, we analyzed nucleosome positioning, H3K27 acetylation, transcription, and gastrulation rates in zebrafish embryos lacking pluripotency factors Pou5f3 and Sox19b. We show that the bulk transcriptional onset does not require Sox19b and Pou5f3, but is sensitive to their balance. Pou5f3 docks H3K27ac on the enhancers of genes involved in gastrulation and ventral fate specification. Sox19b facilitates Pou5f3 access to one-third of these enhancers. The genes regulating mesendodermal and dorsal fates are primed for activation independently on Pou5f3 and Sox19b. Strikingly, the loss of either factor results in activation of silent enhancers; simultaneous loss of both leads to premature expression of differentiation genes. Our results uncover how independent activities of maternal Pou5f3 and Sox19b add up or antagonize to determine the early gene expression repertoire.

Exchanges of histone methylation and variants during mouse zygotic genome activation

Zygote ◽  
2019 ◽  
Vol 28 (1) ◽  
pp. 51-58 ◽  
Author(s):  
Mingtian Deng ◽  
Baobao Chen ◽  
Zifei Liu ◽  
Yu Cai ◽  
Yongjie Wan ◽  
...  
Keyword(s):  
Histone Methylation ◽  
Histone Variants ◽  
Chromatin Accessibility ◽  
Mouse Embryos ◽  
Zygotic Genome Activation ◽  
Male And Female ◽  
Histone 3 ◽  
Female Pronucleus ◽  
Genome Activation ◽  
Zygotic Genome

SummaryMinor and major zygotic genome activation (ZGA) are crucial for preimplantation development. During this process, histone variants and methylation influence chromatin accessibility and consequently regulated the expression of zygotic genes. However, the detailed exchanges of these modifications during ZGA remain to be determined. In the present study, the epigenetic modifications of histone 3 on lysine 9 (H3K9), 27 (H3K27) and 36 (H3K36), as well as four histone variants were determined during minor and major ZGA and in post-ZGA stages of mouse embryos. Firstly, microH2A1, H3K27me3 and H3K36me3 were asymmetrically stained in the female pronucleus during minor ZGA but lost staining in major ZGA. Secondly, H3K9me2 and H3K9me3 were strongly stained in the female pronucleus, but weakly stained in the male pronucleus and disappeared after ZGA. Thirdly, H2A.Z and H3.3 were symmetrically stained in male and female pronuclei during minor ZGA. Moreover, H3K27me2 was not statistically changed during mouse early development, while H3K36me2 was only detected in 2- and 4-cell embryos. In conclusion, our data revealed dynamics of histone methylation and variants during mice ZGA and provided details of their exchange in mice embryogenesis. Moreover, we further inferred that macroH2A1, H2A.Z, H3K9me2/3 and H3K27me2/3 may play crucial roles during mouse ZGA.

scholarly journals The genome-wide multi-layered architecture of chromosome pairing in early Drosophila embryos

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jelena Erceg ◽  
Jumana AlHaj Abed ◽  
Anton Goloborodko ◽  
Bryan R. Lajoie ◽  
Geoffrey Fudenberg ◽  
...  
Keyword(s):  
Computational Approach ◽  
Homologous Chromosomes ◽  
Layered Architecture ◽  
Homolog Pairing ◽  
Genome Wide ◽  
Mammalian Embryos ◽  
Pioneer Factor ◽  
Genome Activation ◽  
Drosophila Embryos ◽  
Zygotic Genome

Abstract Genome organization involves cis and trans chromosomal interactions, both implicated in gene regulation, development, and disease. Here, we focus on trans interactions in Drosophila, where homologous chromosomes are paired in somatic cells from embryogenesis through adulthood. We first address long-standing questions regarding the structure of embryonic homolog pairing and, to this end, develop a haplotype-resolved Hi-C approach to minimize homolog misassignment and thus robustly distinguish trans-homolog from cis contacts. This computational approach, which we call Ohm, reveals pairing to be surprisingly structured genome-wide, with trans-homolog domains, compartments, and interaction peaks, many coinciding with analogous cis features. We also find a significant genome-wide correlation between pairing, transcription during zygotic genome activation, and binding of the pioneer factor Zelda. Our findings reveal a complex, highly structured organization underlying homolog pairing, first discovered a century ago in Drosophila. Finally, we demonstrate the versatility of our haplotype-resolved approach by applying it to mammalian embryos.

scholarly journals CLAMP and Zelda function together to promote Drosophila zygotic genome activation

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jingyue Duan ◽  
Leila Rieder ◽  
Megan M Colonnetta ◽  
Annie Huang ◽  
Mary Mckenney ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Embryonic Development ◽  
Essential Role ◽  
Chromatin Accessibility ◽  
Zygotic Genome Activation ◽  
Zygotic Transcription ◽  
Pioneer Factor ◽  
Pioneer Transcription Factor ◽  
Genome Activation ◽  
Zygotic Genome

During the essential and conserved process of zygotic genome activation (ZGA), chromatin accessibility must increase to promote transcription. Drosophila is a well-established model for defining mechanisms that drive ZGA. Zelda (ZLD) is a key pioneer transcription factor (TF) that promotes ZGA in the Drosophila embryo. However, many genomic loci that contain GA-rich motifs become accessible during ZGA independent of ZLD. Therefore, we hypothesized that other early TFs that function with ZLD have not yet been identified, especially those that are capable of binding to GA-rich motifs such as CLAMP. Here, we demonstrate that Drosophila embryonic development requires maternal CLAMP to: 1) activate zygotic transcription; 2) increase chromatin accessibility at promoters of specific genes that often encode other essential TFs; 3) enhance chromatin accessibility and facilitate ZLD occupancy at a subset of key embryonic promoters. Thus, CLAMP functions as a pioneer factor which plays a targeted yet essential role in ZGA.

scholarly journals Zygotic pioneer factor activity of Odd-paired/Zic is necessary for establishing the Drosophila Segmentation Network

2019 ◽  
Author(s):  
Isabella V. Soluri ◽  
Lauren M. Zumerling ◽  
Omar A. Payan Parra ◽  
Eleanor G. Clark ◽  
Shelby A. Blythe
Keyword(s):  
Regulatory Networks ◽  
Significant Proportion ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Embryonic Patterning ◽  
Network Function ◽  
Pioneer Factor ◽  
Genome Activation ◽  
Pair Rule ◽  
Zygotic Genome

AbstractBecause regulatory networks of transcription factors drive embryonic patterning, it is possible that chromatin accessibility states impact how networks interact with information encoded in DNA. To determine the interplay between chromatin states and regulatory network function, we performed ATAC seq on Drosophila embryos over the period spanning the establishment of the segmentation network, from zygotic genome activation to gastrulation. Chromatin accessibility states are dynamic over this period, and establishment of the segmentation network requires maturation of the ground chromatin state. Elimination of all maternal patterning information allows identification of patterning-dependent and -independent dynamic chromatin regions. A significant proportion of patterning-dependent accessibility stems from pioneer activity of the pair-rule factor Odd-paired (opa). While opa is necessary to drive late opening of segmentation network cis-regulatory elements, competence for opa to pioneer is regulated over time. These results indicate that dynamic systems for chromatin regulation directly impact the interpretation of embryonic patterning information.

scholarly journals Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation

2019 ◽  
Author(s):  
Máté Pálfy ◽  
Gunnar Schulze ◽  
Eivind Valen ◽  
Nadine L. Vastenhouw
Keyword(s):  
Transcription Factors ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Zebrafish Genome ◽  
Zygotic Genome Activation ◽  
Lineage Specification ◽  
Genome Activation ◽  
Zygotic Genome

ABSTRACTIn many organisms, early embryonic development is driven by maternally provided factors until the controlled onset of transcription during zygotic genome activation. The regulation of chromatin accessibility and its relationship to gene activity during this transition remains poorly understood. Here, we generated chromatin accessibility maps from genome activation until the onset of lineage specification. During this period, chromatin accessibility increases at regulatory elements. This increase is independent of RNA polymerase II-mediated transcription, with the exception of the hyper-transcribed miR-430 locus. Instead, accessibility often precedes the transcription of associated genes. Loss of the maternal transcription factors Pou5f3, Sox19b, and Nanog, which are known to be required for zebrafish genome activation, results in decreased accessibility at regulatory elements. Importantly, the accessibility of regulatory regions, especially when established by Pou5f3, Sox19b and Nanog, is predictive for future transcription. Our results show that the maternally provided transcription factors Pou5f3, Sox19b, and Nanog open up chromatin and prime genes for activity during zygotic genome activation in zebrafish.

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.

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