Similar Datasets
Project description:The pioneer transcription factor NR5A2 plays multiple roles in regulating zygotic genome activation and expression of lineage-determining factor during mouse pre-implantation development. However, how NR5A2 differentially regulates transcriptional networks at distinct developmental stages remains unknown. Here, we demonstrate the dynamics of chromatin binding profiles of NR5A2 from the 2-cell to morula stage, which corresponds to totipotency-to-pluripotency transition. Our NR5A2 CUT&Tag analysis identifies lineage-determining factor KLF and GATA families as co-regulators for NR5A2. We find that KLF5 cooperates with NR5A2 to enhance H3K27ac deposition, and NR5A2 predominantly promotes chromatin accessibility. NR5A2 regulates Xist expression either directly or indirectly through its role in up-regulating GATA factor expression. In vitro assays reveal that NR5A2 co-binds to nucleosomes with KLF5 or GATA6, suggesting that these pioneer transcription factors can simultaneously binds to the chromatin. Our findings highlight the role of NR5A2 in ensuring robust gene activation in pre-implantation development through feed-forward regulatory loops with lineage-determining transcription factors.
2025-12-16 | GSE289577 | GEO
Project description:The pioneer transcription factor NR5A2 plays multiple roles in regulating zygotic genome activation and expression of lineage-determining factor during mouse pre-implantation development. However, how NR5A2 differentially regulates transcriptional networks at distinct developmental stages remains unknown. Here, we demonstrate the dynamics of chromatin binding profiles of NR5A2 from the 2-cell to morula stage, which corresponds to totipotency-to-pluripotency transition. Our NR5A2 CUT&Tag analysis identifies lineage-determining factor KLF and GATA families as co-regulators for NR5A2. We find that KLF5 cooperates with NR5A2 to enhance H3K27ac deposition, and NR5A2 predominantly promotes chromatin accessibility. NR5A2 regulates Xist expression either directly or indirectly through its role in up-regulating GATA factor expression. In vitro assays reveal that NR5A2 co-binds to nucleosomes with KLF5 or GATA6, suggesting that these pioneer transcription factors can simultaneously binds to the chromatin. Our findings highlight the role of NR5A2 in ensuring robust gene activation in pre-implantation development through feed-forward regulatory loops with lineage-determining transcription factors.
2025-12-16 | GSE289573 | GEO
Project description:The pioneer transcription factor NR5A2 plays multiple roles in regulating zygotic genome activation and expression of lineage-determining factor during mouse pre-implantation development. However, how NR5A2 differentially regulates transcriptional networks at distinct developmental stages remains unknown. Here, we demonstrate the dynamics of chromatin binding profiles of NR5A2 from the 2-cell to morula stage, which corresponds to totipotency-to-pluripotency transition. Our NR5A2 CUT&Tag analysis identifies lineage-determining factor KLF and GATA families as co-regulators for NR5A2. We find that KLF5 cooperates with NR5A2 to enhance H3K27ac deposition, and NR5A2 predominantly promotes chromatin accessibility. NR5A2 regulates Xist expression either directly or indirectly through its role in up-regulating GATA factor expression. In vitro assays reveal that NR5A2 co-binds to nucleosomes with KLF5 or GATA6, suggesting that these pioneer transcription factors can simultaneously binds to the chromatin. Our findings highlight the role of NR5A2 in ensuring robust gene activation in pre-implantation development through feed-forward regulatory loops with lineage-determining transcription factors.
2025-12-16 | GSE289568 | GEO
Project description:Feed-forward regulatory loops by NR5A2 ensure robust gene activation during pre-implantation development
| PRJNA1223456 | ENA
Project description:Feed-forward regulatory loops by NR5A2 ensure robust gene activation during pre-implantation development [ATAC-seq]
| PRJNA1223447 | ENA
Project description:Feed-forward regulatory loops by NR5A2 ensure robust gene activation during pre-implantation development [RNA-seq]
| PRJNA1223463 | ENA
Project description:Feed-forward regulatory loops by NR5A2 ensure robust gene activation during pre-implantation development [CUT&Tag, CUT&RUN, TIP-seq]
| PRJNA1223450 | ENA
Project description:The regulatory relationships between genes and proteins in a cell form a gene regulatory network (GRN) that controls the cellular response to changes in the environment. A number of inference methods to reverse engineer the original GRN from large-scale expression data have recently been developed. However, the absence of ground-truth GRNs when evaluating the performance makes realistic simulations of GRNs necessary. One aspect of this is that local network motif analysis of real GRNs indicates that the feed-forward loop (FFL) is significantly enriched. To simulate this properly, we developed a novel motif-based preferential attachment algorithm, FFLatt, which outperformed the popular GeneNetWeaver network generation tool in reproducing the FFL motif occurrence observed in literature-based biological GRNs. It also preserves important topological properties such as scale-free topology, sparsity, and average in/out-degree per node. We conclude that FFLatt is well-suited as a network generation module for a benchmarking framework with the aim to provide fair and robust performance evaluation of GRN inference methods.
| S-EPMC8872634 | biostudies-literature
Project description:Network motifs, such as the feed-forward loop (FFL), introduce a range of complex behaviors to transcriptional regulatory networks, yet such properties are typically determined from their isolated study. We characterize the effects of crosstalk on FFL dynamics by modeling the cross regulation between two different FFLs and evaluate the extent to which these patterns occur in vivo. Analytical modeling suggests that crosstalk should overwhelmingly affect individual protein-expression dynamics. Counter to this expectation we find that entire FFLs are more likely than expected to resist the effects of crosstalk (≈20% for one crosstalk interaction) and remain dynamically modular. The likelihood that cross-linked FFLs are dynamically correlated increases monotonically with additional crosstalk, but is independent of the specific regulation type or connectivity of the interactions. Just one additional regulatory interaction is sufficient to drive the FFL dynamics to a statistically different state. Despite the potential for modularity between sparsely connected network motifs, Escherichia coli (E. coli) appears to favor crosstalk wherein at least one of the cross-linked FFLs remains modular. A gene ontology analysis reveals that stress response processes are significantly overrepresented in the cross-linked motifs found within E. coli. Although the daunting complexity of biological networks affects the dynamical properties of individual network motifs, some resist and remain modular, seemingly insulated from extrinsic perturbations-an intriguing possibility for nature to consistently and reliably provide certain network functionalities wherever the need arise.
| S-EPMC5406374 | biostudies-literature
Project description:Idiopathic pulmonary fibrosis is a progressive scarring disease characterized by extracellular matrix accumulation and altered mechanical properties of lung tissue. Recent studies support the hypothesis that these compositional and mechanical changes create a progressive feed-forward loop in which enhanced matrix deposition and tissue stiffening contribute to fibroblast and myofibroblast differentiation and activation, which further perpetuates matrix production and stiffening. The biomechanical properties of tissues are sensed and responded to by mechanotransduction pathways that facilitate sensing of changes in mechanical cues by tissue resident cells and convert the mechanical signals into downstream biochemical signals. Although our understanding of mechanotransduction pathways associated with pulmonary fibrosis remains incomplete, recent progress has allowed us to begin to elucidate the specific mechanisms supporting fibrotic feed-forward loops. The mechanosensors discussed here include integrins, Piezo channels, transient receptor potential channels, and nonselective ion channels. Also discussed are downstream transcription factors, including myocardin-related transcription factor and Yes-associated protein/transcriptional coactivator with PDZ-binding motif. This review describes mechanosensors and mechanotransduction pathways associated with fibrosis progression and highlights promising therapeutic insights.
| S-EPMC7768346 | biostudies-literature