H2AK119ub1 guides maternal inheritance and zygotic deposition of H3K27me3 in mouse embryos
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA642853 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12109000.fastq.gz | Fastqsanger.gz | |||
| SRR12109001.fastq.gz | Fastqsanger.gz | |||
| SRR12109002.fastq.gz | Fastqsanger.gz | |||
| SRR12108947_1.fastq.gz | Fastqsanger.gz | |||
| SRR12108947_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 93 |
Similar Datasets
Project description:Parental epigenomes are established during gametogenesis. While they are largely reset soon after fertilization in mammals, maternal histone H3 tri-methylation at lysine 27 (H3K27me3) is inherited by the next generation embryos. How H3K27me3 is properly established in oocytes and passed on to the embryos remains elusive. Furthermore, although polycomb repressive complex 2 (PRC2)-mediated H3K27me3 is known to interplay with PRC1-mediated mono-ubiquitination of histone H2A at lysine 119 (H2AK119ub1) to coordinate repressive polycomb domains in embryonic stem cells (ESCs), how they act in vivo remains unknown. To address these questions, here we profiled H2AK119ub1 dynamics during mouse oogenesis and preimplantation development, and investigated its functions in maternal inheritance of H3K27me3. Integrative analyses with H3K27me3 dynamics revealed that an unusually broad and distal-rich distribution of H2AK119ub1 is established during oogenesis and co-transmitted to embryos together with H3K27me3. On the other hand, an ESC-like canonical distribution of H2AK119ub1 is newly established at the 2-cell stage, a few days earlier than that of H3K27me3. Deficiency in polycomb group ring finger 1 (PCGF1) and PCGF6, essential components of variant PRC1 (vPRC1), leads to massive reduction of H2AK119ub1 and gene-selective loss of H3K27me3 in oocytes. The gene-selective deficient state of H3K27me3 is irreversibly inherited by embryos, which causes bi-allelic expression of H3K27me3-dependent imprinted genes, including Xist, embryonic sublethality, and placental enlargement at term. Collectively, our study not only revealed instructive in vivo dynamics of H2AK119ub1 for H3K27me3 establishment at the maternal-to-embryonic transition, but also identified PCGF1/6-PRC1 as an essential player for intergenerational epigenetic inheritance.
2021-01-31 | GSE153496 | GEO
Project description:Maternal-to-zygotic transition (MZT) is the first and key step in the control of animal development and is intimately related to changes of chromatin structure and histone modifications. Mono-ubiquitination of histone H2A at lysine-119 (H2AK119ub1), an important epigenetic modification in regulating chromatin configuration and function, is primarily catalyzed by polycomb repressive complex 1 (PRC1) and contributes to resistance to transcriptional reprogramming in mouse embryos. In this study, the genome-wide dynamic distribution of H2AK119ub1 during MZT in mice was investigated by chromosome immunoprecipitation and sequencing. The results indicated that H2AK119ub1 accumulated in fully grown oocytes, enriched at the transcriptional start sequences (TSSs) of maternal genes, but was promptly removed after meiotic resumption, particularly at the TSSs of early zygotic genes, by a previously unidentified mechanism. Genetic evidences indicated that ubiquitin-specific peptidase 16 (USP16) is the major deubiquitinase of H2AK119ub1 in mouse oocytes. Conditional knockout of Usp16 in oocytes did not impair their survival, growth, andor meiotic maturation. However, oocytes lacking USP16 were unable to undergo zygotic genome activation or gain developmental competence after fertilization, due to high levels of H2AK119ub1 deposition on the zygotic genomes. Taken together, this study indicates that H2AK119ub1 is erased during oocyte maturation by an USP16-dependent mechanism, which ensures zygotic genome reprogramming and transcriptional activation of essential early zygotic genes.
2022-06-05 | GSE154412 | GEO
Project description:Ubiquitin-specific protease 7 (USP7) has been implicated in cancer progression and neurodevelopment. However, its molecular targets remain poorly characterized. We combined quantitative proteomics, transcriptomics, and epigenomics to define the core USP7 network. Our multi-omics analysis reveals USP7 as a control hub that links genome regulation, tumor suppression, and histone H2A ubiquitylation (H2AK119ub1) by noncanonical Polycomb-repressive complexes (ncPRC1s). USP7 strongly stabilizes ncPRC1.6 and, to a lesser extent, ncPRC1.1. Moreover, USP7 represses expression of AUTS2, which suppresses H2A ubiquitylation by ncPRC1.3/5. Collectively, these USP7 activities promote the genomic deposition of H2AK119ub1 by ncPRC1, especially at transcriptionally repressed loci. Notably, USP7-dependent changes in H2AK119ub1 levels are uncoupled from H3K27me3. Even complete loss of the PRC1 catalytic core and H2AK119ub1 has only a limited effect on H3K27me3. Besides defining the USP7 regulome, our results reveal that H2AK119ub1 dosage is largely disconnected from H3K27me3.
2022-11-12 | GSE217658 | GEO
Project description:Ubiquitin-specific protease 7 (USP7) has been implicated in cancer progression and neurodevelopment. However, its molecular targets remain poorly characterized. We combined quantitative proteomics, transcriptomics, and epigenomics to define the core USP7 network. Our multi-omics analysis reveals USP7 as a control hub that links genome regulation, tumor suppression, and histone H2A ubiquitylation (H2AK119ub1) by noncanonical Polycomb-repressive complexes (ncPRC1s). USP7 strongly stabilizes ncPRC1.6 and, to a lesser extent, ncPRC1.1. Moreover, USP7 represses expression of AUTS2, which suppresses H2A ubiquitylation by ncPRC1.3/5. Collectively, these USP7 activities promote the genomic deposition of H2AK119ub1 by ncPRC1, especially at transcriptionally repressed loci. Notably, USP7-dependent changes in H2AK119ub1 levels are uncoupled from H3K27me3. Even complete loss of the PRC1 catalytic core and H2AK119ub1 has only a limited effect on H3K27me3. Besides defining the USP7 regulome, our results reveal that H2AK119ub1 dosage is largely disconnected from H3K27me3.
2022-11-08 | GSE193019 | GEO
Project description:Ubiquitin-specific protease 7 (USP7) has been implicated in cancer progression and neurodevelopment. However, its molecular targets remain poorly characterized. We combined quantitative proteomics, transcriptomics, and epigenomics to define the core USP7 network. Our multi-omics analysis reveals USP7 as a control hub that links genome regulation, tumor suppression, and histone H2A ubiquitylation (H2AK119ub1) by noncanonical Polycomb-repressive complexes (ncPRC1s). USP7 strongly stabilizes ncPRC1.6 and, to a lesser extent, ncPRC1.1. Moreover, USP7 represses expression of AUTS2, which suppresses H2A ubiquitylation by ncPRC1.3/5. Collectively, these USP7 activities promote the genomic deposition of H2AK119ub1 by ncPRC1, especially at transcriptionally repressed loci. Notably, USP7-dependent changes in H2AK119ub1 levels are uncoupled from H3K27me3. Even complete loss of the PRC1 catalytic core and H2AK119ub1 has only a limited effect on H3K27me3. Besides defining the USP7 regulome, our results reveal that H2AK119ub1 dosage is largely disconnected from H3K27me3.
2022-11-08 | GSE193014 | GEO
Project description:Ubiquitin-specific protease 7 (USP7) has been implicated in cancer progression and neurodevelopment. However, its molecular targets remain poorly characterized. We combined quantitative proteomics, transcriptomics, and epigenomics to define the core USP7 network. Our multi-omics analysis reveals USP7 as a control hub that links genome regulation, tumor suppression, and histone H2A ubiquitylation (H2AK119ub1) by noncanonical Polycomb-repressive complexes (ncPRC1s). USP7 strongly stabilizes ncPRC1.6 and, to a lesser extent, ncPRC1.1. Moreover, USP7 represses expression of AUTS2, which suppresses H2A ubiquitylation by ncPRC1.3/5. Collectively, these USP7 activities promote the genomic deposition of H2AK119ub1 by ncPRC1, especially at transcriptionally repressed loci. Notably, USP7-dependent changes in H2AK119ub1 levels are uncoupled from H3K27me3. Even complete loss of the PRC1 catalytic core and H2AK119ub1 has only a limited effect on H3K27me3. Besides defining the USP7 regulome, our results reveal that H2AK119ub1 dosage is largely disconnected from H3K27me3.
2022-11-08 | GSE193013 | GEO
Project description:Pseudouridine guides germline small RNA transport and epigenetic inheritance.
| PRJNA960809 | ENA
Project description:BAP1 is recurrently mutated or deleted in a large number of diverse cancer types, including mesothelioma, uveal melanoma and hepatocellular cholangiocarcinoma. BAP1 is the catalytic subunit of the Polycomb Repressive De-Ubiquitination complex (PR-DUB) which removes PRC1 mediated H2AK119ub1. We and others have shown that H2AK119ub1 is essential for maintaining transcriptional repression and contributes to PRC2 chromatin recruitment. However, the precise relationship between BAP1 and PRC1 remains mechanistically elusive. Using embryonic stem cells, we show that a major function of BAP1 is to restrict H2AK119ub1 deposition to target sites. This increases the stability of PcG complexes with their targets and prevents diffuse accumulation of H2AK119ub1 and H3K27me3 modifications. Loss of BAP1 results in a broad increase in H2AK119ub1 levels that are primarily dependent on PCGF3/5-PRC1 complexes with a mechanism that is reminiscent of X-chromosome inactivation. Increased genome-wide H2AK119ub1 levels titrates away PRC2 from its targets and stimulates diffuse H3K27me3 accumulation across the genome. This decreases the activity of PcG repressive machineries at physiological targets and induces a general compaction of the entire chromatin. Our findings provide evidences for a unifying model that resolves the apparent contradiction between BAP1 catalytic activity and its role in vivo, uncovering molecular vulnerabilities that could be useful for BAP1-related pathologies.
2021-06-27 | GSE162739 | GEO
Project description:Heritable gene silencing is essential for the development of multicellular organisms. Polycomb repressive complexes 1 and 2 (PRC1 and 2) catalyze and recognize histone H2A lysine 119 mono-ubiquitination (H2AK119ub1) and histone H3 lysine 27 trimethylation (H3K27me3), respectively, to mediate heritable gene silencing, but the mechanism of inheritance is not fully understood. Using an inducible gene silencing strategy, we show that the epigenetic inheritance of Polycomb silencing in human cells is strongly dependent on local DNA sequences and chromatin environment. In addition, we find that inheritance is not strictly dependent on H3K27me3 recognition and can be partially achieved by H2AK119ub1 catalysis and recognition, independently of H3K27me3. These findings demonstrate that locus specific features and H2AK119ub1 play key roles in inheritance of Polycomb silencing in human cells.
2024-05-15 | GSE209986 | GEO
Project description:Pseudouridine guides small RNA transport and inheritance via Exportin-t
| PRJNA956931 | ENA