The impact of retrotransposons on zygotic genome activation and the chromatin landscape of early embryos DOI Creative Commons
Therese Solberg, Mie Kobayashi‐Ishihara, Haruhiko Siomi

и другие.

Annals of the New York Academy of Sciences, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 22, 2024

Abstract In mammals, fertilization is followed by extensive reprogramming and reorganization of the chromatin accompanying transcriptional activation embryo. This results in blastomeres with ability to give rise all cell types a complete organism, including extra‐embryonic tissues, known as totipotency. Transcriptional occurs process zygotic genome (ZGA) tightly linked expression transposable elements, endogenous retroviruses (ERVs) such retrovirus leucine tRNA primer (ERVL). Recent studies discovered importance ERVs this process, yet race decipher network surrounding these elements still ongoing, molecular mechanism behind their involvement remains mystery. Amid recent surge reporting discovery various factors pathways involved regulation ERVs, review provides an overview knowns unknowns field, particular emphasis on landscape how shape preimplantation development mammals. so doing, we highlight discoveries that have advanced our understanding are transforming quiescent zygote into most powerful type

Язык: Английский

Endogenous retroviruses mediate transcriptional rewiring in response to oncogenic signaling in colorectal cancer DOI Creative Commons
Atma M. Ivancevic, David Simpson,

Olivia Joyner

и другие.

Science Advances, Год журнала: 2024, Номер 10(29)

Опубликована: Июль 17, 2024

Cancer cells exhibit rewired transcriptional regulatory networks that promote tumor growth and survival. However, the mechanisms underlying formation of these pathological remain poorly understood. Through a pan-cancer epigenomic analysis, we found primate-specific endogenous retroviruses (ERVs) are rich source enhancers displaying cancer-specific activity. In colorectal cancer other epithelial tumors, oncogenic MAPK/AP1 signaling drives activation derived from ERV family LTR10. Functional studies in revealed LTR10 elements regulate tumor-specific expression multiple genes associated with tumorigenesis, such as ATG12 XRCC4 . Within human population, individual germline somatic structural variation resulting highly mutable internal tandem repeat region, which affects AP1 binding Our findings reveal ERV-derived contribute to dysregulation response shape evolution networks.

Язык: Английский

Процитировано

11
Epigenome dynamics in early mammalian embryogenesis DOI

Adam Burton,

Maria‐Elena Torres‐Padilla

Nature Reviews Genetics, Год журнала: 2025, Номер unknown

Опубликована: Апрель 3, 2025

Язык: Английский

Процитировано

1
Rise and SINE: roles of transcription factors and retrotransposons in zygotic genome activation DOI
Pavel Kravchenko, Kikuë Tachibana

Nature Reviews Molecular Cell Biology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 2, 2024

Язык: Английский

Процитировано

6
Pioneer Transcription Factors: The First Domino in Zygotic Genome Activation DOI Creative Commons
Bo Fu, Hong Ma, Di Liu

и другие.

Biomolecules, Год журнала: 2024, Номер 14(6), С. 720 - 720

Опубликована: Июнь 18, 2024

Zygotic genome activation (ZGA) is a pivotal event in mammalian embryogenesis, marking the transition from maternal to zygotic control of development. During ZGA process that characterized by intricate cascade gene expression, who tipped first domino meticulously arranged sequence subject paramount interest. Recently, Dux, Obox and Nr5a2 were identified as pioneer transcription factors reside at top transcriptional hierarchy. Through co-option retrotransposon elements hubs for activation, these rewire regulatory network, thus initiating ZGA. In this review, we provide snapshot mechanisms underlying functions factors. We propose starting point where embryo’s own begins influence development trajectory, therefore in-depth dissecting during will form cornerstone our understanding early embryonic development, which pave way advancing grasp developmental biology optimizing vitro production (IVP) techniques.

Язык: Английский

Процитировано

3
Kick-starting the zygotic genome: licensors, specifiers, and beyond DOI Creative Commons
Zhuoning Zou, Qiuyan Wang, Xi Wu

и другие.

EMBO Reports, Год журнала: 2024, Номер 25(10), С. 4113 - 4130

Опубликована: Авг. 19, 2024

Zygotic genome activation (ZGA), the first transcription event following fertilization, kickstarts embryonic program that takes over control of early development from maternal products. How ZGA occurs, especially in mammals, is poorly understood due to limited amount research materials. With rapid single-cell and low-input technologies, remarkable progress made past decade has unveiled dramatic transitions epigenomes, transcriptomes, proteomes, metabolomes associated with ZGA. Moreover, functional investigations are yielding insights into key regulators ZGA, among which two major classes players emerging: licensors specifiers. Licensors would permission its timing during Accumulating evidence suggests such include apparatus nuclear gatekeepers. Specifiers instruct specific genes These specifiers factors present at this stage, often facilitated by epigenetic regulators. Based on data primarily mammals but also results other species, we discuss review how recent sheds light molecular regulation executors, including

Язык: Английский

Процитировано

3
Transposition element MERVL regulates DNA demethylation through TET3 in oxidative-damaged mouse preimplantation embryos DOI Creative Commons
Lihong Liu, Siyao Ha, Dan Cao

и другие.

Molecular Medicine, Год журнала: 2025, Номер 31(1)

Опубликована: Март 12, 2025

Abstract Transposable elements (TEs) comprise approximately half of eukaryotic genomes and significantly contribute to genome plasticity. In this study, we focused on a specific TE, MERVL, which exhibits particular expression during the 2-cell stage commonly serves as an indicator embryonic totipotency. However, its precise role in embryo development remains mysterious. We utilized DRUG-seq investigate effects oxidative damage genes TEs expression. Our findings revealed that exposure hydrogen peroxide (H 2 O ) could induce DNA damage, apoptosis, incomplete demethylation embryos, were potentially associated with MERVL To further explore function, antisense nucleotides (ASO) targeting constructed knockdown early embryos. Notably, led occurrence apoptosis stage, consequently reducing number embryos progress blastocyst stage. Moreover, discovered exerted influence reprogramming methylation. MERVL-deficient activity demethylase ten-eleven translocation 3 (TET3) was suppressed, resulting impaired when compared normal development. This impairment might underpin mechanism impacts Collectively, our study not only verified crucial but also probed regulatory function methylation reprogramming, thereby laying solid foundation for investigations into MERVL's role.

Язык: Английский

Процитировано

0
DUX-mediated configuration of p300/CBP drives minor zygotic genome activation independent of its catalytic activity DOI Creative Commons
Lieying Xiao, Hao Jin, Yanna Dang

и другие.

Cell Reports, Год журнала: 2025, Номер 44(4), С. 115544 - 115544

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
The maternal-to-zygotic transition: reprogramming of the cytoplasm and nucleus DOI
Mina Kojima, Caroline Hoppe, Antonio J. Giráldez

и другие.

Nature Reviews Genetics, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 25, 2024

Язык: Английский

Процитировано

1
CRISPRa-mediated disentanglement of the Dux-MERVL axis in the 2C-like state, totipotency and cell death DOI Creative Commons
Paul Chammas,

Sheila Q. Xie,

Lessly P. Sepulveda-Rincon

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 25, 2024

Transposable elements (TEs) provide sequences that are powerful cis-regulatory drivers of gene expression programmes. This is particularly apparent during early development when many TEs become de-repressed. MERVL highly yet transiently upregulated in mouse totipotent 2-cell (2C) embryos major zygotic genome activation (ZGA), and 2C-like cells vitro. One the most activators pioneer transcription factor, Dux. However, differences lie requirement for Dux versus embryos, unclear reasons. Moreover, sustained causes cell toxicity multiple types, which may or not be linked to activation. Using a CRISPR-activation, 2C-GFP reporter system, we have unpicked relative role ZGA, totipotent-like characteristics toxicity. We find direct comprises only portion Dux-dependent transcriptome, sufficient expanded fate potential, but other totipotency features. Conversely, Dux-induced pathology independent involves induction pro-apoptotic Noxa. Our study highlights complexity Dux-MERVL transcriptional network uncovers new player Dux-driven pathology.

Язык: Английский

Процитировано

0
BMAL1 represses transposable elements independently of CLOCK in pluripotent cells DOI Open Access
Amador Gallardo, Efres Belmonte‐Reche, María Marti-Marimon

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 18, 2024

Abstract Circadian oscillations of gene transcripts rely on a negative feedback loop executed by the activating BMAL1-CLOCK heterodimer and its regulators PER CRY. Although circadian rhythms CLOCK protein are mostly absent during embryogenesis, lack BMAL1 prenatal development causes an early aging phenotype adulthood, suggesting that carries out unknown non-circadian function organism is fundamental for healthy adult life. Here, we show interacts with TRIM28 represses transcription totipotency-associated MERVL retrotransposons in mouse pluripotent cells. Deletion Bmal1 leads to genome-wide upregulation MERVLs, changes three-dimensional organization genome, acquisition features. Overall, demonstrate cells redeployed as transcriptional repressor transposable elements (TEs) CLOCK-independent way. We propose BMAL1-TRIM28 activity life essential optimal health span mammals.

Язык: Английский

Процитировано

0