OBOX regulates murine zygotic genome activation and early development
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ABSTRACT:
PROVIDER: PRJNA890651 | ENA |
REPOSITORIES: ENA
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Project description:Zygotic genome activation (ZGA) activates the quiescent genome to enable the maternal-to-zygotic transition. However, the identity of transcription factors (TFs) that underlie mammalian ZGA in vivo remains unresolved. Here, we showed that OBOX, a PRD-like homeobox domain TF family that includes 66 members (OBOX1-8), are key regulators of mouse ZGA. Knockout mice deficient for maternally transcribed Obox1/2/5/7 and zygotically expressed Obox3/4 led to 2-4 cell arrest accompanied by impaired ZGA. Maternal and zygotic expressed OBOX redundantly support embryonic development as Obox KO defects can be rescued by restoring either of them. Chromatin binding analysis revealed Obox knockout preferentially affected OBOX-binding targets. Mechanistically, OBOX facilitated RNA Pol II ?pre-configuration?, as Pol II relocates from the initial 1-cell binding targets to ZGA gene promoters and distal enhancers. The impaired Pol II pre-configuration in Obox mutants was accompanied by downregulation of ZGA genes, chromatin accessibility transition defects, as well as aberrant activation of one-cell Pol II targets. Finally, OBOX ectopically activated ZGA genes and MERVL in mESCs. Hence, these data demonstrate that OBOX regulates murine ZGA and early embryogenesis.
2023-04-24 | GSE215813 | GEO
Project description:NR5A2 bridges zygotic genome activation to lineage segregation in early mouse development
| PRJNA903396 | ENA
Project description:Histone variant H2A.Z regulates zygotic genome activation
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Project description:Understanding the factors that regulate the transition from oocyte to embryo is critical for determining how cells are reprogrammed to become totipotent or pluripotent. Although factors that can reprogram somatic cells into induced pluripotent stem cells have been discovered, we have limited information regarding how this process occurs physiologically in vivo. Here we identified a specific mediator complex subunit, the kinase domain subunit MED13, as being recruited for translation during oocyte maturation and transcribed very early from the zygotic genome. Both knockdown and conditional knockout genetic approaches demonstrate that MED13 is absolutely essential for zygotic genome activation in the mouse in part through regulation of the embryo-specific chromatin remodeling complex, esBAF. This role is mediated by interactions with E2F family transcription factors. In addition to MED13, its paralog, MED13L, is also required for successful preimplantation embryo development. Although MED13L can partially compensate for loss of MED13 function, post-implantation embryo development is not rescued by MED13L because the pluripotency factor NANOG is not expressed at normal levels. Our data demonstrate for the first time an essential role for MED13 in supporting chromatin reprogramming and directed transcription of essential genes during zygotic genome activation
2019-11-29 | GSE90710 | GEO
Project description:Precocious expression of Zelda does not initiate early zygotic genome activation
| PRJNA811124 | ENA
Project description:Mammalian early embryo development incorporates a series of processes including maternal-to-zygotic transition (MZT), zygotic genome activation (ZGA) and lineage specification etc., coupled with totipotency decline and pluripotency formation. Identification of transcription factors (TFs) orchestrating these processes remains challenging. In this study, by taking advantages of targeted protein degron system in mice, which enabled us to study TF stage-specific functions in vivo, we identified and validated the Gabpa is not only a regulator of major ZGA, but also plays an essential role in epiblast lineage specification and pluripotency formation. GABPA together with other reported pluripotency regulators plays major roles in a stepwise manner during the pluripotency formation, highlighting a dynamic multi-factorial pluripotency regulation network throughout mammalian pre-implantation development.
2024-09-17 | GSE263171 | GEO
Project description:During the first stages of development, the fertilized germ cells rapidly transition to totipotency. Maternally deposited mRNAs encode the proteins necessary for reprogramming the transcriptionally quiescent zygotic genome during this maternal-to-zygotic transition (MZT). The transcription factor Zelda is essential for this reprogramming in the Drosophila embryo. Zelda is necessary for transcriptional activation of the zygotic genome, and the absence of Zelda leads to embryonic lethality during the MZT. Excess Zelda activity is also lethal to the embryo, demonstrating that Zelda levels must be precisely controlled during early development. Because Zelda is encoded by a maternally deposited mRNA, Zelda levels in the embryo are controlled at the level of translation. To understand how levels of this essential reprogramming factor were regulated to allow for embryonic development and zygotic genome activation, we investigated the factors that regulated translation of zelda. Brain Tumor (BRAT) is a translational regulator that was previously shown to bind to zelda mRNA in the embryo. We showed that BRAT functions to repress zelda translation, as embryos deficient for maternal BRAT activity prematurely express Zelda. We further showed that in the larval brain, BRAT similarly regulates Zelda levels and identified specific BRAT-binding sites that mediate these effects. Thus, BRAT regulates Zelda in multiple tissues. Because both too little and too much Zelda are lethal to the embryo, we hypothesized that precocious expression of this transcriptional activator might be capable of driving precocious activation of the zygotic genome, leading to embryonic lethality. To test this hypothesis, we performed single embryo RNA-seq at distinct nuclear cycles throughout zygotic genome activation (NC10, NC12, NC13, and NC14) in control and brat-mutant embryos. Our results conclusively demonstrated that in embryos lacking functional BRAT, Zelda target genes were not prematurely activated. Rather, these genes were expressed normally, but become significantly upregulated at nuclear cycle 14, when the division cycle slows. Our data support a model in which zygotic genome activation requires precise coordination between expression of reprogramming factors, such as Zelda, and the slowing of the cell cycle.
2022-06-17 | GSE197582 | GEO
Project description:Maternal transcription factor TCF12 mediates fertilization and zygotic genome activation during early embryonic development
| PRJNA869723 | ENA
Project description:GABPA regulates zygotic genome activation and pluripotency formation
| PRJNA1096032 | ENA
Project description:After fertilization, zygotic genome activation (ZGA) enables the conversion of two terminally differentiated gametes to a totipotent embryo. Zygotes further give rise to the pluripotent embryonic lineages and extraembryonic trophectoderm after the first lineage commitment. While much is learned for pluripotency regulation, how ZGA is connected to the pluripotency commitment in early embryos remains unclear. Here, we investigated the role of nuclear receptor (NR) family TFs in mouse pre-implantation embryos, whose motifs are highly enriched in accessible chromatin at the 2-cell (2C) to 8-cell (8C) stages. We found NR5A2 is required for the early development, as both knockdown and knockout of Nr5a2 led to morula arrest. 4-8C activated genes (mid-preimplantation activation), including key pluripotency marker genes (i.e. Nanog, Pou5f1, and Tdgf1) and trophectoderm genes (i.e. Klf5, Elf3, and Gata3). Genome-wide chromatin binding and RNA-seq analyses showed NR5A2 bound and regulated the 4-8C genes, including both ICM and TE genes in 2C and 8C embryos , indicating its roles in bipotency program. Interestingly, NR5A2 occupied sites predominantly reside in accessible B1 elements where its motif is embedded at the 2-8C stage. Taken together, these data demonstrate the role of NR5A2 as a key regulator that bridges ZGA to lineage segregation.
2022-12-07 | GSE218379 | GEO