Faculty Opinions recommendation of Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation.

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.

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GAF is essential for zygotic genome activation and chromatin accessibility in the early Drosophila embryo

eLife ◽

10.7554/elife.66668 ◽

2021 ◽

Vol 10 ◽

Author(s):

Marissa M Gaskill ◽

Tyler J Gibson ◽

Elizabeth D Larson ◽

Melissa M Harrison

Keyword(s):

Chromatin Accessibility ◽

Drosophila Embryo ◽

Gaga Factor ◽

Zygotic Transcription ◽

Early Drosophila Embryo ◽

Zygotic Gene ◽

Pioneer Factor ◽

Pioneer Factors ◽

Genome Activation ◽

Development Proceeds

Following fertilization, the genomes of the germ cells are reprogrammed to form the totipotent embryo. Pioneer transcription factors are essential for remodeling the chromatin and driving the initial wave of zygotic gene expression. In Drosophila melanogaster, the pioneer factor Zelda is essential for development through this dramatic period of reprogramming, known as the maternal-to-zygotic transition (MZT). However, it was unknown whether additional pioneer factors were required for this transition. We identified an additional maternally encoded factor required for development through the MZT, GAGA Factor (GAF). GAF is necessary to activate widespread zygotic transcription and to remodel the chromatin accessibility landscape. We demonstrated that Zelda preferentially controls expression of the earliest transcribed genes, while genes expressed during widespread activation are predominantly dependent on GAF. Thus, progression through the MZT requires coordination of multiple pioneer-like factors, and we propose that as development proceeds control is gradually transferred from Zelda to GAF.

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

Nature Communications ◽

10.1038/s41467-021-26234-7 ◽

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.

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

10.1101/2020.11.23.394171 ◽

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.

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Exchanges of histone methylation and variants during mouse zygotic genome activation

Zygote ◽

10.1017/s0967199419000649 ◽

2019 ◽

Vol 28 (1) ◽

pp. 51-58 ◽

Cited By ~ 1

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.

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CLAMP and Zelda function together to promote Drosophila zygotic genome activation

eLife ◽

10.7554/elife.69937 ◽

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.

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The pioneer factor GAF is essential for zygotic genome activation and chromatin accessibility in the early Drosophila embryo

10.1101/2020.07.15.204248 ◽

2020 ◽

Author(s):

Marissa M. Gaskill ◽

Tyler J. Gibson ◽

Elizabeth D. Larson ◽

Melissa M. Harrison

Keyword(s):

Transcriptional Control ◽

Chromatin Accessibility ◽

Drosophila Embryo ◽

Gaga Factor ◽

Zygotic Transcription ◽

Early Drosophila Embryo ◽

Zygotic Gene ◽

Pioneer Factor ◽

Pioneer Factors ◽

Genome Activation

AbstractFollowing fertilization, the genomes of the germ cells are reprogrammed to form the totipotent embryo. Pioneer transcription factors are required for remodeling the chromatin and driving the initial wave of zygotic gene expression. In Drosophila melanogaster, the pioneer factor Zelda is essential for development through this dramatic period of reprogramming, known as the maternal- to-zygotic transition (MZT). However, it was unknown whether additional pioneer factors were necessary for this transition. We identified an additional maternally encoded factor required for development through the MZT, GAGA Factor (GAF). GAF is needed to activate widespread zygotic transcription and to remodel the chromatin accessibility landscape. We demonstrated that Zelda preferentially controls expression of the earliest transcribed genes, while genes expressed during widespread activation are predominantly dependent on GAF. Thus, progression through the MZT requires coordination of multiple pioneer factors, and we propose that as development proceeds transcriptional control is gradually transferred from Zelda to GAF.

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

10.1101/852707 ◽

2019 ◽

Cited By ~ 1

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.

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

10.1101/2021.03.18.436074 ◽

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.

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