Epigenetic Reprogramming in Early Animal Development

Cold Spring Harbor Perspectives in Biology, Год журнала: 2021, Номер 14(6), С. a039677 - a039677

Опубликована: Авг. 16, 2021

Dramatic nuclear reorganization occurs during early development to convert terminally differentiated gametes a totipotent zygote, which then gives rise an embryo. Aberrant epigenome resetting severely impairs embryo and even leads lethality. How the epigenomes are inherited, reprogrammed, reestablished in this critical developmental period has gradually been unveiled through rapid of technologies including ultrasensitive chromatin analysis methods. In review, we summarize latest findings on epigenetic reprogramming gametogenesis embryogenesis, how it contributes gamete maturation parental-to-zygotic transition. Finally, highlight key questions that remain be answered fully understand regulation development.

Язык: Английский

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SLAMseq resolves the kinetics of maternal and zygotic gene expression during early zebrafish embryogenesis

Cell Reports, Год журнала: 2023, Номер 42(2), С. 112070 - 112070

Опубликована: Фев. 1, 2023

The maternal-to-zygotic transition (MZT) is a key developmental process in metazoan embryos that involves the activation of zygotic transcription (ZGA) and degradation maternal transcripts. We employed metabolic mRNA sequencing (SLAMseq) to deconvolute compound embryonic transcriptome zebrafish. While mitochondrial transcripts prevail prior MZT, we uncover spurious hundreds short intron-poor genes as early 2-cell stage. Upon ZGA, most originate from thousands maternal-zygotic (MZ) are transcribed at rates comparable those purely replenish mRNAs distinct timescales. Rapid replacement MZ transcript decay features unrelated major pathways promotes de novo synthesis core gene expression machinery by increasing poly(A)-tail length translation efficiency. SLAMseq hence provides insights into timescales, molecular features, regulation MZT during zebrafish embryogenesis.

Язык: Английский

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Real-time single-molecule imaging of transcriptional regulatory networks in living cells

Nature Reviews Genetics, Год журнала: 2024, Номер 25(4), С. 272 - 285

Опубликована: Янв. 9, 2024

Язык: Английский

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Detection of newly synthesized RNA reveals transcriptional reprogramming during ZGA and a role of Obox3 in totipotency acquisition

Cell Reports, Год журнала: 2024, Номер 43(4), С. 114118 - 114118

Опубликована: Апрель 1, 2024

Zygotic genome activation (ZGA) after fertilization enables the maternal-to-zygotic transition. However, global view of ZGA, particularly at initiation, is incompletely understood. Here, we develop a method to capture and sequence newly synthesized RNA in early mouse embryos, providing transcriptional reprogramming during ZGA. Our data demonstrate that major ZGA gene begins earlier than previously thought. Furthermore, identify set genes activated minor promoters which show enrichment Obox factor motif, find Obox3 or Obox5 overexpression embryonic stem cells activates genes. Notably, expression factors severely impaired somatic cell nuclear transfer (SCNT) restoration corrects profile greatly improves SCNT embryo development. Hence, our study reveals dynamic underscores crucial role facilitating totipotency acquisition.

Язык: Английский

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The Dynamics of Histone Modifications during Mammalian Zygotic Genome Activation

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1459 - 1459

Опубликована: Янв. 25, 2024

Mammalian fertilization initiates the reprogramming of oocytes and sperm, forming a totipotent zygote. During this intricate process, zygotic genome undergoes maternal-to-zygotic transition (MZT) subsequent activation (ZGA), marking initiation transcriptional control gene expression post-fertilization. Histone modifications are pivotal in shaping cellular identity many mammals. Recent advances chromatin analysis have enabled detailed explorations histone during ZGA. This review delves into conserved unique regulatory strategies, providing essential insights dynamic changes their variants ZGA The objective is to explore recent advancements leading mechanisms related governing embryonic development phase depth. These considerations will be useful for informing future therapeutic approaches that target epigenetic regulation diverse biological contexts. It also contribute extensive areas evolutionary developmental biology possibly lay foundation research discussion on seminal topic.

Язык: Английский

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Transcription bodies regulate gene expression by sequestering CDK9

Nature Cell Biology, Год журнала: 2024, Номер 26(4), С. 604 - 612

Опубликована: Апрель 1, 2024

Abstract The localization of transcriptional activity in specialized transcription bodies is a hallmark gene expression eukaryotic cells. It remains unclear, however, if and how affect expression. Here we disrupted the formation two prominent endogenous that mark onset zygotic zebrafish embryos analysed effect on using enriched SLAM-seq live-cell imaging. We find disruption results misregulation hundreds genes. focus genes are upregulated. These have accessible chromatin poised to be transcribed presence bodies, but they do not go into elongation. Live-cell imaging shows large enables these ectopic suggesting sequester pause release factor. Supporting this hypothesis, CDK9—the kinase releases paused polymerase II—is highly bodies. Overexpression CDK9 wild-type thus phenocopies removal Taken together, our show regulate by sequestering machinery, thereby preventing elsewhere nucleus from being transcribed.

Язык: Английский

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Live-cell imaging reveals the spatiotemporal organization of endogenous RNA polymerase II phosphorylation at a single gene

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Май 26, 2021

The carboxyl-terminal domain of RNA polymerase II (RNAP2) is phosphorylated during transcription in eukaryotic cells. While residue-specific phosphorylation has been mapped with exquisite spatial resolution along the 1D genome a population fixed cells using immunoprecipitation-based assays, timing, kinetics, and organization single-copy gene have not yet measured living Here, we achieve this by combining multi-color, single-molecule microscopy fluorescent antibody-based probes that specifically bind to different forms endogenous RNAP2 Applying methodology HIV-1 reporter provides live-cell evidence for heterogeneity distribution length as well Serine 5 clusters remain separated both space time from nascent mRNA synthesis. Computational models determine 40 cluster around promoter typical transcriptional burst, most at within 6 seconds arrival roughly half escaping ~1.5 minutes. Taken together, our data provide support notion efficient transiently form promoters contain high concentrations 5.

Язык: Английский

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Brainstem circuits encoding start, speed, and duration of swimming in adult zebrafish

Neuron, Год журнала: 2022, Номер 111(3), С. 372 - 386.e4

Опубликована: Ноя. 21, 2022

The flexibility of locomotor movements requires an accurate control their start, duration, and speed. How brainstem circuits encode convey these parameters remains unclear. Here, we have combined in vivo calcium imaging, electrophysiology, anatomy, behavior adult zebrafish to address questions. We reveal that the detailed are encoded by two molecularly, topographically, functionally segregated glutamatergic neuron subpopulations within nucleus medial longitudinal fasciculus. changes locomotion speed vGlut2+ neurons, whereas vGlut1+ neurons sudden high speed/high amplitude movements. Ablation compromised slow-explorative swimming, ablation impaired fast swimming. Our results provide mechanistic insights into how separate implement flexible commands. These command suitably organized integrate environmental cues hence generate swimming match animal's behavioral needs.

Язык: Английский

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Live-cell imaging uncovers the relationship between histone acetylation, transcription initiation, and nucleosome mobility

Science Advances, Год журнала: 2023, Номер 9(40)

Опубликована: Окт. 4, 2023

Histone acetylation and RNA polymerase II phosphorylation are associated with transcriptionally active chromatin, but their spatiotemporal relationship in live cells remains poorly understood. To address this problem, we combine Fab-based labeling of endogenous protein modifications single-molecule tracking to quantify the dynamics chromatin enriched histone H3 lysine-27 (H3K27ac) serine-5 (RNAP2-Ser5ph). Our analysis reveals that these two is generally separate. In separated sites, show inversely correlated one another on minutes time scale single nucleosomes within each region display distinct opposing subsecond scale. While diffuse ~15% faster H3K27ac, they slower RNAP2-Ser5ph. These results argue high levels H3K27ac RNAP2-Ser5ph not often present together at same place time, rather marks poised or respectively.

Язык: Английский

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Acetylation of histones and non-histone proteins is not a mere consequence of ongoing transcription

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июнь 11, 2024

In all eukaryotes, acetylation of histone lysine residues correlates with transcription activation. Whether is a cause or consequence debated. One model suggests that promotes the recruitment and/or activation acetyltransferases, and occurs as ongoing transcription. However, extent to which shapes global protein landscapes not known. Here, we show remains virtually unaltered after acute inhibition. Transcription inhibition ablates co-transcriptionally occurring ubiquitylation H2BK120 but does reduce acetylation. The combined CBP/p300 further demonstrates acetyltransferases remain active continue acetylate histones independently Together, these results mere transcription; acetyltransferase are uncoupled from act transcription, non-histone sustained in absence

Язык: Английский

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