Human embryonic genome activation initiates at the one-cell stage DOI Creative Commons
Maki Asami, Brian Lam, Marcella Ma

et al.

Cell stem cell, Journal Year: 2021, Volume and Issue: 29(2), P. 209 - 216.e4

Published: Dec. 21, 2021

In human embryos, the initiation of transcription (embryonic genome activation [EGA]) occurs by eight-cell stage, but its exact timing and profile are unclear. To address this, we profiled gene expression at depth in metaphase II oocytes bipronuclear (2PN) one-cell embryos. High-resolution single-cell RNA sequencing revealed previously inaccessible oocyte-to-embryo changes. This confirmed transcript depletion following fertilization (maternal degradation) also uncovered low-magnitude upregulation hundreds spliced transcripts. Gene analysis predicted embryonic processes including cell-cycle progression chromosome maintenance as well transcriptional activators that included cancer-associated regulators. Transcription was disrupted abnormal monopronuclear (1PN) tripronuclear (3PN) These findings indicate initiates sooner than thought. The pattern promises to illuminate involved onset development, with implications for epigenetic inheritance, stem-cell-derived cancer.

Language: Английский

ATAC-seq footprinting unravels kinetics of transcription factor binding during zygotic genome activation DOI Creative Commons
Mette Bentsen, Philipp Goymann, Hendrik Schultheis

et al.

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Aug. 26, 2020

Abstract While footprinting analysis of ATAC-seq data can theoretically enable investigation transcription factor (TF) binding, the lack a computational tool able to conduct different levels has so-far hindered widespread application this method. Here we present TOBIAS, comprehensive, accurate, and fast framework enabling genome-wide TF binding dynamics for hundreds TFs simultaneously. We validate TOBIAS using paired ChIP-seq data, find that outperforms existing methods bias correction footprinting. As proof-of-concept, illustrate how unveil complex during zygotic genome activation in both humans mice, propose Dux activates cascades TFs, binds repeat elements induces expression novel genetic elements.

Language: Английский

Citations

508

Mechanisms regulating zygotic genome activation DOI
Katharine N. Schulz, Melissa M. Harrison

Nature Reviews Genetics, Journal Year: 2018, Volume and Issue: 20(4), P. 221 - 234

Published: Dec. 20, 2018

Language: Английский

Citations

459

Roles and regulation of histone methylation in animal development DOI
Ashwini Jambhekar, Abhinav Dhall, Yang Shi

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2019, Volume and Issue: 20(10), P. 625 - 641

Published: July 2, 2019

Language: Английский

Citations

449

The maternal-to-zygotic transition revisited DOI Open Access
Nadine L. Vastenhouw,

Wen Xi Cao,

Howard D. Lipshitz

et al.

Development, Journal Year: 2019, Volume and Issue: 146(11)

Published: June 1, 2019

The development of animal embryos is initially directed by maternal gene products. Then, during the maternal-to-zygotic transition (MZT), developmental control handed to zygotic genome. Extensive research in both vertebrate and invertebrate model organisms has revealed that MZT can be subdivided into two phases, which very different modes regulation are implemented: initially, exclusively post-transcriptional post-translational, following gradual activation genome leads predominance transcriptional regulation. These changes expression program precisely controlled highly interconnected. Here, we review current understanding mechanisms underlie handover MZT.

Language: Английский

Citations

379

Molecular mechanisms of transgenerational epigenetic inheritance DOI
Maximilian Fitz-James, Giacomo Cavalli

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(6), P. 325 - 341

Published: Jan. 4, 2022

Language: Английский

Citations

374

Resetting histone modifications during human parental-to-zygotic transition DOI Open Access
Weikun Xia, Jiawei Xu, Guang Yu

et al.

Science, Journal Year: 2019, Volume and Issue: 365(6451), P. 353 - 360

Published: July 4, 2019

Histone modifications regulate gene expression and development. To address how they are reprogrammed in human early development, we investigated key histone marks oocytes embryos. Unlike that mouse oocytes, the permissive mark trimethylated H3 lysine 4 (H3K4me3) largely exhibits canonical patterns at promoters oocytes. After fertilization, prezygotic genome activation (pre-ZGA) embryos acquire chromatin widespread H3K4me3 CpG-rich regulatory regions. By contrast, repressive H3K27me3 undergoes global depletion. regions then resolve to either active or repressed states upon ZGA, followed by subsequent restoration of developmental genes. Finally, combining transcriptome maps, revealed transcription circuitry asymmetric patterning during lineage specification. Collectively, our data unveil a priming phase connecting parental-to-zygotic epigenetic transition.

Language: Английский

Citations

216

Chromatin plasticity: A versatile landscape that underlies cell fate and identity DOI Open Access
Tejas Yadav, Jean‐Pierre Quivy, Geneviève Almouzni

et al.

Science, Journal Year: 2018, Volume and Issue: 361(6409), P. 1332 - 1336

Published: Sept. 28, 2018

During development and throughout life, a variety of specialized cells must be generated to ensure the proper function each tissue organ. Chromatin plays key role in determining cellular state, whether totipotent, pluripotent, multipotent, or differentiated. We highlight chromatin dynamics involved generation pluripotent stem as well their influence on cell fate decision reprogramming. focus capacity histone variants, chaperones, modifications, heterochromatin factors identity its plasticity. Recent technological advances have provided tools elucidate underlying for better understanding normal pathological conditions, with avenues potential therapeutic application.

Language: Английский

Citations

185

Single-cell multi-omics sequencing of human early embryos DOI
Lin Li, Fan Guo, Yun Gao

et al.

Nature Cell Biology, Journal Year: 2018, Volume and Issue: 20(7), P. 847 - 858

Published: June 15, 2018

Language: Английский

Citations

181

Reprogramming roadmap reveals route to human induced trophoblast stem cells DOI
Xiaodong Liu, John F. Ouyang, Fernando J. Rossello

et al.

Nature, Journal Year: 2020, Volume and Issue: 586(7827), P. 101 - 107

Published: Sept. 16, 2020

Language: Английский

Citations

179

Insights into epigenetic patterns in mammalian early embryos DOI Creative Commons
Ruimin Xu, Chong Li, Xiaoyu Liu

et al.

Protein & Cell, Journal Year: 2020, Volume and Issue: 12(1), P. 7 - 28

Published: July 15, 2020

Mammalian fertilization begins with the fusion of two specialized gametes, followed by major epigenetic remodeling leading to formation a totipotent embryo. During development pre-implantation embryo, precise reprogramming progress is prerequisite for avoiding developmental defects or embryonic lethality, but underlying molecular mechanisms remain elusive. For past few years, unprecedented breakthroughs have been made in mapping regulatory network dynamic epigenomes during mammalian early embryo development, taking advantage multiple advances and innovations low-input genome-wide chromatin analysis technologies. The aim this review highlight most recent understanding embryogenesis mammals, including DNA methylation, histone modifications, accessibility 3D organization.

Language: Английский

Citations

164