GABPA regulates zygotic genome activation and pluripotency formation
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ABSTRACT:
PROVIDER: PRJNA1096032 | ENA |
REPOSITORIES: ENA
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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:[PROJECT] After fertilization the embryonic genome is inactive until transcription is initiated during the maternal-zygotic transition (MZT). This universal process coincides with the formation of pluripotent cells, which in mammals can be used to generate embryonic stem (ES) cells. To study the changes in chromatin structure that accompany zygotic genome activation and pluripotency, we mapped the genomic locations of histone H3 modifications before and after MZT in zebrafish embryos. Repressive H3 lysine 27 trimethylation (H3K27me3) and activating H3 lysine 4 trimethylation (H3K4me3) are only detected after MZT. H3K4me3 marks more than 80% of genes, including many developmental regulatory genes that are also occupied by H3K27me3. Sequential chromatin immunoprecipitation demonstrates that both methylation marks occupy the same promoter regions, revealing that the bivalent chromatin domains found in cultured ES cells also exist in embryos. In addition, we find a large group of genes that are monovalently marked by H3K4me3 but not H3K27me3. These H3K4me3 monovalent genes are neither expressed nor stably bound by RNA polymerase II. Closer inspection of in vitro data sets reveals similar monovalent H3K4me3 domains in ES cells. The analysis of an inducible transgene indicates that H3K4me3 domains can form in the absence of sequence-specific transcriptional activators or stable association with RNA pol II. These results suggest that bivalent and monovalent domains might poise embryonic genes for activation and that the chromatin profile associated with pluripotency is established during MZT. [SAMPLES] ChIPchip analysis of histone modifications (H3K4me3, H3K27me3, H3K36me3) and RNA polymerase II in pre MZT (256-cell) and post MZT (4hpf; dome/30% epiboly) wt zebrafish embryos. H3K4me3, H3K27me3, H3K36me3 and PolII ChIP-chip at 256 cell stage (one replicate) and 4hpf (dome/30% epiboly) (two replicates)
2010-01-25 | E-GEOD-20023 | biostudies-arrayexpress
Project description:Histone variant H2A.Z regulates zygotic genome activation
| PRJNA678804 | ENA
Project description:[PROJECT] After fertilization the embryonic genome is inactive until transcription is initiated during the maternal-zygotic transition (MZT). This universal process coincides with the formation of pluripotent cells, which in mammals can be used to generate embryonic stem (ES) cells. To study the changes in chromatin structure that accompany zygotic genome activation and pluripotency, we mapped the genomic locations of histone H3 modifications before and after MZT in zebrafish embryos. Repressive H3 lysine 27 trimethylation (H3K27me3) and activating H3 lysine 4 trimethylation (H3K4me3) are only detected after MZT. H3K4me3 marks more than 80% of genes, including many developmental regulatory genes that are also occupied by H3K27me3. Sequential chromatin immunoprecipitation demonstrates that both methylation marks occupy the same promoter regions, revealing that the bivalent chromatin domains found in cultured ES cells also exist in embryos. In addition, we find a large group of genes that are monovalently marked by H3K4me3 but not H3K27me3. These H3K4me3 monovalent genes are neither expressed nor stably bound by RNA polymerase II. Closer inspection of in vitro data sets reveals similar monovalent H3K4me3 domains in ES cells. The analysis of an inducible transgene indicates that H3K4me3 domains can form in the absence of sequence-specific transcriptional activators or stable association with RNA pol II. These results suggest that bivalent and monovalent domains might poise embryonic genes for activation and that the chromatin profile associated with pluripotency is established during MZT. [SAMPLES] ChIPchip analysis of histone modifications (H3K4me3, H3K27me3, H3K36me3) and RNA polymerase II in pre MZT (256-cell) and post MZT (4hpf; dome/30% epiboly) wt zebrafish embryos.
2010-01-26 | GSE20023 | GEO
Project description:Upon fertilization, the embryonic genome remains transcriptionally inactive until the mid-blastula transition. Zygotic genome activation (ZGA) of vertebrate embryos has been extensively studied using nucleic acid-based strategies, but proteomics data are still scarce, impeding the full mechanistic understanding of how ZGA is executed during the maternal-to-zygotic transition (MZT). Here, we performed quantitative proteomics to decipher the proteome landscape of zebrafish embryos during the MZT, quantifying nearly 5,000 proteins across four embryonic stages. The stage-specific clustering based on protein expression pattern revealed that helicases (i.e., eif4a2 and ruvbl1) facilitate pluripotency factors (i.e., nanog, pou5f3, ctcf, and hmga1) triggering ZGA in zebrafish, accompanied by the maternal product decay with P-bodies and ubiquitin dependent proteolytic pathway. Dozens of transcription factors show wave-like expression patterns during MZT, implying their diverse functions in triggering the ZGA and modulating differentiation for organ development. The combination of morpholino knockdown and quantitative proteomics demonstrated that maternal Nanog is required for proper embryogenesis by regulating 1) interactions with other pluripotency factors, 2) F-actin band formation, 3) cell cycle checkpoints and 4) maternal product degradation. This study represents the most systematic proteomics survey of developmentally regulated proteins and their expression profiles accompanying MZT in zebrafish, which is a valuable proteome resource for understanding ZGA.
2024-05-01 | PXD036678 | Pride
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:Maternal KLF17 regulates zygotic genome activation in the mouse
| PRJNA872350 | ENA
Project description:OBOX regulates murine zygotic genome activation and early development
| PRJNA890651 | ENA
Project description:Upon fertilization, maternal factors direct development in a transcriptionally silent embryo. At the maternal-to-zygotic transition (MZT), a universal step in animal development, unknown maternal factors trigger zygotic genome activation (ZGA). In zebrafish, ZGA is required for gastrulation and clearance of maternal mRNAs, which is achieved in part by the conserved microRNA miR-430. However, the precise factors that activate the zygotic program remain largely unknown. Here we show that Nanog, Pou5f1 and SoxB1 are required for genome activation in zebrafish. We identified several hundred genes directly activated by maternal factors, thus constituting the first wave of zygotic transcription in zebrafish. Ribosome profiling in the pre-MZT embryo revealed that nanog, sox19b and pou5f1 are the most highly translated transcription factor mRNAs. Combined loss of function for Nanog, SoxB1 and Pou5f1 resulted in developmental arrest prior to gastrulation, and a failure to activate >75% of zygotic genes. Furthermore, we found that Nanog binds the miR-430 locus and together with Pou5f1 and SoxB1 initiate miR-430 expression and activity. Our results demonstrate that maternal Nanog, Pou5f1 and SoxB1 are required to initiate the zygotic developmental program and in turn trigger the clearance of the maternal program by activating miR-430 expression. Wild type and loss-of-function total mRNA sequencing of embryonic transcriptomes pre- and post-MZT; ribosome profiling pre-MZT
2013-09-22 | E-GEOD-47558 | biostudies-arrayexpress
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