Interaction network of human early embryonic transcription factors
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive Hybrid Quadrupole-Orbitrap
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: 
Markku Varjosalo
PROVIDER: MSV000091321 | MassIVE | Sat Feb 18 03:19:00 GMT 2023
REPOSITORIES: MassIVE
Similar Datasets
Project description:Embryonic genome activation (EGA) occurs during preimplantation development and is characterized by the initiation of de novo transcription from the embryonic genome. Despite its importance, the regulation of EGA and the transcription factors involved in this process are poorly understood. Paired-like homeobox (PRDL) family proteins are implicated as potential transcriptional regulators of EGA, yet the PRDL-mediated gene regulatory networks remain uncharacterized. To investigate the function of PRDL proteins, we are identifying the molecular interactions and the functions of a subset family of the Eutherian Totipotent Cell Homeobox (ETCHbox) proteins, seven PRDL family proteins and six other transcription factors (TFs), all suggested to participate in transcriptional regulation during preimplantation. Using mass spectrometry-based interactomics methods, AP-MS and proximity-dependent biotin labeling, and chromatin immunoprecipitation sequencing we derive the comprehensive regulatory networks of these preimplantation TFs. By these interactomics tools we identify more than a thousand high-confidence interactions for the 21 studied bait proteins with more than 300 interacting proteins. We also establish that TPRX2, currently assigned as pseudogene, is a transcriptional activator.
| S-EPMC10933267 | biostudies-literature
Project description:Transcription factors (TFs) engage in protein-protein interactions throughout the process of transcriptional control. In this study, we have successfully identified the protein-protein interactions for more than 100 distinct human transcription factors (TFs) using the techniques of proximity-dependent biotinylation (BioID) and affinity purification mass spectrometry (AP-MS).
| MSV000092891 | MassIVE
Project description:PCR and MiSeq validation for early embryonic substitution candidates from 400 Breast cancer patients
| EGAS00001001218 | EGA
Project description:BACKGROUND: Gene regulatory networks control the global gene expression and the dynamics of protein output in living cells. In multicellular organisms, transcription factors and microRNAs are the major families of gene regulators. Recent studies have suggested that these two kinds of regulators share similar regulatory logics and participate in cooperative activities in the gene regulatory network; however, their combinational regulatory effects and preferences on the protein interaction network remain unclear. METHODS: In this study, we constructed a global human gene regulatory network comprising both transcriptional and post-transcriptional regulatory relationships, and integrated the protein interactome into this network. We then screened the integrated network for four types of regulatory motifs: single-regulation, co-regulation, crosstalk, and independent, and investigated their topological properties in the protein interaction network. RESULTS: Among the four types of network motifs, the crosstalk was found to have the most enriched protein-protein interactions in their downstream regulatory targets. The topological properties of these motifs also revealed that they target crucial proteins in the protein interaction network and may serve important roles of biological functions. CONCLUSIONS: Altogether, these results reveal the combinatorial regulatory patterns of transcription factors and microRNAs on the protein interactome, and provide further evidence to suggest the connection between gene regulatory network and protein interaction network.
| S-EPMC3337275 | biostudies-literature
Project description:The Yin Yang 1 (YY1) transcription factor is a master regulator of development, essential for early embryogenesis and adult tissues formation. YY1 is the mammalian orthologue of Pleiohomeotic, one of the transcription factors that binds Polycomb DNA response elements in Drosophila melanogaster and mediates Polycomb group proteins (PcG) recruitment to DNA. Despite several publications pointing at YY1 having a similar role in mammalians, others showed features of YY1 that are not compatible with PcG functions. Here, we show that, in mouse Embryonic Stem (ES) cells, YY1 has genome-wide PcG-independent activities while it is still stably associated with the INO80 chromatin-remodeling complex, as well as with novel RNA helicase activities. YY1 binds chromatin in close proximity of the transcription start site of highly expressed genes. Loss of YY1 functions preferentially led to a down-regulation of target genes expression, as well as to an up-regulation of several small non-coding RNAs, suggesting a role for YY1 in regulating small RNA biogenesis. Finally, we found that YY1 is a novel player of Myc-related transcription factors and that its coordinated binding at promoters potentiates gene expression, proposing YY1 as an active component of the Myc transcription network that links ES to cancer cells.
| S-EPMC3333890 | biostudies-literature
Project description:Microsporidia are ubiquitous parasites that infect a wide range of animal hosts, and these fungal-related microbes undergo their entire replicative lifecycle inside of host cells. Despite being widespread in the environment and causing medical and agricultural harm, virtually nothing is known about the host factors important to facilitate their growth and development inside of host cells. Here, we perform a genetic screen to identify host transcription factors important for development of the microsporidian pathogen Nematocida parisii inside intestinal cells of its natural host, the nematode Caenorhabditis elegans Through this screen, we identified the C. elegans Myc family of transcription factors as key host regulators of microsporidia growth and development. The Mad-like transcription factor MDL-1, and the Max-like transcription factors MXL-1 and MXL-2 promote pathogen levels, while the Myc-Mondo-like transcription factor MML-1 inhibits pathogen levels. We used epistasis analysis to show that MDL-1 and MXL-1, which are thought to function as a heterodimer, appear to be acting canonically. In contrast, MXL-2 and MML-1, which are also thought to function as a heterodimer, appear to be acting in separate pathways (noncanonically) in the context of pathogen infection. We also found that both MDL-1::GFP and MML-1::GFP are expressed in intestinal cells during infection. These findings provide novel insight into the host transcription factors that regulate microsporidia development.
| S-EPMC5015929 | biostudies-literature
Project description:mouse embryonic fibroblasts, embryonic stem cells, and induced pluripotent stem cells were compared via metabolomic analysis
2018-08-02 | MSV000082680 | GNPS
Project description:Laparoscopic colon surgery has been performed widely. As a minimal invasive approach, single incision (Embryonic NOTES) colon surgery has been attempted.
However, there are not sufficient evidences for single incision colon surgery in colon cancer.
The investigators are researching the efficacy and safety of single incision laparoscopic sigmoidectomy in sigmoid colon cancer.
| 2100226 | ecrin-mdr-crc
Project description:Continuous, non-cell cycle-dependent expression of cyclin E is a characteristic feature of mouse embryonic stem cells (mESCs). We studied the 5' regulatory region of Cyclin E, also known as Ccne1, and identified binding sites for transcription factors of the naïve pluripotency network, including Esrrb, Klf4, and Tfcp2l1 within 1 kilobase upstream of the transcription start site. Luciferase assay and chromatin immunoprecipitation-quantitative polymerase chain reaction (ChiP-qPCR) study highlighted one binding site for Esrrb that is essential to transcriptional activity of the promoter region, and three binding sites for Klf4 and Tfcp2l1. Knockdown of Esrrb, Klf4, and Tfcp2l1 reduced Cyclin E expression whereas overexpression of Esrrb and Klf4 increased it, indicating a strong correlation between the expression level of these factors and that of cyclin E. We observed that cyclin E overexpression delays differentiation induced by Esrrb depletion, suggesting that cyclin E is an important target of Esrrb for differentiation blockade. We observed that mESCs express a low level of miR-15a and that transfection of a miR-15a mimic decreases Cyclin E mRNA level. These results lead to the conclusion that the high expression level of Cyclin E in mESCs can be attributed to transcriptional activation by Esrrb as well as to the absence of its negative regulator, miR-15a.
| S-EPMC6773236 | biostudies-literature
Project description:Pluripotency maintenance requires transcription factors (TFs) that induce genes necessary to preserve the undifferentiated state and repress others involved in differentiation. Recent observations support that the heterogeneous distribution of TFs in the nucleus impacts on gene expression. Thus, it is essential to explore how TFs dynamically organize to fully understand their role in transcription regulation. Here, we examine the distribution of pluripotency TFs Oct4 and Sox2 in the nucleus of embryonic stem (ES) cells and inquire whether their organization changes during early differentiation stages preceding their downregulation. Using ES cells expressing Oct4-YPet or Sox2-YPet, we show that Oct4 and Sox2 partition between nucleoplasm and a few chromatin-dense foci which restructure after inducing differentiation by 2i/LIF withdrawal. Fluorescence correlation spectroscopy showed distinct changes in Oct4 and Sox2 dynamics after differentiation induction. Specifically, we detected an impairment of Oct4-chromatin interactions whereas Sox2 only showed slight variations in its short-lived, and probably more unspecific, interactions with chromatin. Our results reveal that differentiation cues trigger early changes of Oct4 and Sox2 nuclear distributions that also include modifications in TF-chromatin interactions. This dynamical reorganization precedes Oct4 and Sox2 downregulation and may contribute to modulate their function at early differentiation stages.
| S-EPMC7089971 | biostudies-literature