Protein interaction networks of human transcription factors
Ontology highlight
ABSTRACT:
INSTRUMENT(S): timsTOF Pro 2
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: 
Markku Varjosalo
PROVIDER: MSV000092891 | MassIVE |
REPOSITORIES: MassIVE
Similar Datasets
Project description:How transcription factors (TFs), the ultimate targets and executors of cellular signalling pathways, are regulated via protein-protein interactions remains elusive. To systematically investigate the regulations and functions of human transcription factors, we performed proteomics studies of soluble and chromatin-associated complexes of 56 TFs in HEK293T cells, using tandem-affinity-purification followed by mass spectrometry (TAP/MS). We performed 214 purifications and identified 2,156 high-confident protein-protein interactions.
2015-04-07 | PXD001383 | Pride
Project description:The Nuclear Factor I (NFI) family of transcription factors (TFs) plays key roles in cellular differentiation, proliferation, and homeostasis. As such, NFI family members engage in large number of interactions with other proteins and the chromatin. However, despite their well-established significance, the NFIs interactomes, their dynamics, and their functions have not been comprehensively examined. Here, we employed complementary omics-level techniques, i.e. interactomics (affinity purification mass spectrometry (AP-MS) and proximity-dependent biotinylation (BioID)), and chromatin immunoprecipitation sequencing (ChIP-Seq), to obtain a comprehensive view of the NFI proteins and their interactions. Our analyses included all four main NFI family members, and a less studied short isoform of NFIB (NFIB4), which lacks the DNA binding domain. We observed that, despite exhibiting some redundancy, each family member had unique high-confidence interactors and target genes, highlighting distinct roles within the transcriptional regulatory networks. The study revealed that NFIs interact with a large number of other TFs to co-regulate a broad range of regulatory networks and cellular processes. Notably, time-dependent proximity-labeling unveiled a highly dynamic nature of NFI protein-protein interaction networks and hinted at temporal modulation of NFI interactions. Furthermore, gene ontology (GO) enrichment analysis of NFI interactome and targetome revealed the involvement of NFIs in transcriptional regulation, chromatin organization, and cellular signaling pathways, and pathways related with cancer. Additionally, we observed that NFIB4 engages with proteins associated with mRNA regulation, which suggests that NFIs have roles beyond traditional DNA binding and transcriptional modulation. We propose that NFIs serve as pioneering TFs, playing critical roles in regulating other TFs and influencing a wide range of cellular processes. These insights into NFI protein-protein interactions and their dynamic, context-dependent nature provide a deeper understanding of gene regulation mechanisms and hint at the role of NFIs as master regulators.
2024-06-26 | MSV000095163 | MassIVE
Project description:Mammalian gene expression is controlled by transcription factors (TFs) that engage sequence motifs in a chromatinized genome, where nucleosomes can restrict DNA access. Yet, how nucleosomes affect individual TFs remains unclear. Here, we measure the ability of over one hundred TF motifs to recruit TFs in a defined chromosomal locus in mouse embryonic stem cells. This identifies a set sufficient to enable binding of TFs with diverse tissue specificities, functions, and DNA binding domains. These chromatin-competent factors are further classified when challenged to engage motifs within a highly-phased nucleosome. The pluripotency factors OCT4- SOX2 preferentially engage non-nucleosomal and entry-exit motifs, but not nucleosome internal sites, a preference that also guides binding genome-wide. By contrast, factors such as BANP, REST, or CTCF, engage throughout causing nucleosomal displacement.This reveals that TFs vary widely in their sensitivity to nucleosomes and that genome access is TF-specific and influenced by nucleosome position in the cell.
2024-08-13 | GSE240647 | GEO
Project description:Mammalian gene expression is controlled by transcription factors (TFs) that engage sequence motifs in a chromatinized genome, where nucleosomes can restrict DNA access. Yet, how nucleosomes affect individual TFs remains unclear. Here, we measure the ability of over one hundred TF motifs to recruit TFs in a defined chromosomal locus in mouse embryonic stem cells. This identifies a set sufficient to enable binding of TFs with diverse tissue specificities, functions, and DNA binding domains. These chromatin-competent factors are further classified when challenged to engage motifs within a highly-phased nucleosome. The pluripotency factors OCT4- SOX2 preferentially engage non-nucleosomal and entry-exit motifs, but not nucleosome internal sites, a preference that also guides binding genome-wide. By contrast, factors such as BANP, REST, or CTCF, engage throughout causing nucleosomal displacement.This reveals that TFs vary widely in their sensitivity to nucleosomes and that genome access is TF-specific and influenced by nucleosome position in the cell.
2024-08-13 | GSE242066 | GEO
Project description:Transcription factors (TFs) orchestrate the gene expression programs that define each cell’s identity, and the canonical TF accomplishes this with two functional domains1–7. The DNA-binding domain interacts with specific genomic sequences, and the effector domain binds coactivators or co-repressors that contribute to transcriptional regulation. We report here that TFs also frequently contain an RNA-binding domain and that this also contributes to gene regulation. Nearly half of TFs in human cells show evidence of RNA-binding and their affinities for RNA are similar to those of well-studied RNA-binding proteins. The RNA-binding sites of TFs have sequence and functional features analogous to the arginine-rich motif of the HIV transcriptional activator Tat8,9. RNA-binding contributes to TF function by promoting the dynamic association of TFs with chromatin. We conclude that the canonical definition of transcription factors is incomplete, and that the ability of many TFs to bind DNA, RNA and protein is fundamental to gene regulation.
2023-07-02 | PXD035484 | Pride
Project description:Precise dissection of DNA-protein interactions is essential for elucidating recognition basis, dynamics, and gene regulation mechanism. However, global profiling of weak and dynamic DNA-protein interactions remains a long-standing challenge. Here, we establish light-induced lysine (K) enabled crosslinking (LIKE-XL) strategy for spatiotemporal and global profiling of DNA-protein interactions. Harnessing the unique abilities to capture weak and transient DNA-protein interactions, we demonstrate that LIKE-XL enables discovery of low-affinity transcription factors (TFs)-DNA interactions via sequence-specific DNA baits, determining the binding sites for TFs previously unachieved. More importantly, we successfully decipher the dynamics of TF subproteome in response to drug treatment in time-resolved manner, and find new downstream target TFs from drug perturbations, providing insights into their dynamic transcriptional networks. The LIKE-XL offers a novel and complementary method to expand the DNA-protein profiling toolbox and map accurate DNA-protein interactomes previously inaccessible via noncovalent strategies, for better understanding of protein functions in health and disease.
2023-01-03 | PXD039229 |
Project description:The DNA-binding activities of transcription factors (TFs) are influenced by both intrinsic sequence preferences and extrinsic interactions with cell-specific chromatin landscapes and other regulatory proteins. Disentangling the roles of these determinants in TF-DNA binding remains challenging. For instance, the FoxA subfamily of Forkhead domain TFs are known pioneer factors, yet their binding varies across cell types, pointing to a combination of intrinsic and extrinsic forces guiding their binding. How such sequence and chromatin influences vary across related Forkhead domain TFs remains mostly uncharacterized. Here, we present a principled approach to compare the relative contributions of intrinsic DNA sequence preference and cell-specific chromatin environments to a TF’s DNA-binding activities. We over-express a selection of Fox TFs in mouse embryonic stem (mES) cells, which offer a platform to contrast each TF's binding activity within the same preexisting chromatin background. By developing and applying a neural network that jointly models sequence and chromatin data, we can evaluate how sequence and preexisting chromatin features contribute to induced TF binding, both at individual sites and genome-wide. We demonstrate that Fox TFs bind different DNA targets, and drive differential gene expression patterns, even when induced in identical chromatin settings. Differential Fox binding activities can be attributed to distinct DNA-binding preferences coupled with differential abilities to engage relatively inaccessible chromatin. We propose that varying preferences for preexisting chromatin states enables the functional diversification of paralogous TFs.
2023-10-04 | GSE244410 | GEO
Project description:The DNA-binding activities of transcription factors (TFs) are influenced by both intrinsic sequence preferences and extrinsic interactions with cell-specific chromatin landscapes and other regulatory proteins. Disentangling the roles of these determinants in TF-DNA binding remains challenging. For instance, the FoxA subfamily of Forkhead domain TFs are known pioneer factors, yet their binding varies across cell types, pointing to a combination of intrinsic and extrinsic forces guiding their binding. How such sequence and chromatin influences vary across related Forkhead domain TFs remains mostly uncharacterized. Here, we present a principled approach to compare the relative contributions of intrinsic DNA sequence preference and cell-specific chromatin environments to a TF’s DNA-binding activities. We over-express a selection of Fox TFs in mouse embryonic stem (mES) cells, which offer a platform to contrast each TF's binding activity within the same preexisting chromatin background. By developing and applying a neural network that jointly models sequence and chromatin data, we can evaluate how sequence and preexisting chromatin features contribute to induced TF binding, both at individual sites and genome-wide. We demonstrate that Fox TFs bind different DNA targets, and drive differential gene expression patterns, even when induced in identical chromatin settings. Differential Fox binding activities can be attributed to distinct DNA-binding preferences coupled with differential abilities to engage relatively inaccessible chromatin. We propose that varying preferences for preexisting chromatin states enables the functional diversification of paralogous TFs.
2023-10-04 | GSE244409 | GEO
Project description:The DNA-binding activities of transcription factors (TFs) are influenced by both intrinsic sequence preferences and extrinsic interactions with cell-specific chromatin landscapes and other regulatory proteins. Disentangling the roles of these determinants in TF-DNA binding remains challenging. For instance, the FoxA subfamily of Forkhead domain TFs are known pioneer factors, yet their binding varies across cell types, pointing to a combination of intrinsic and extrinsic forces guiding their binding. How such sequence and chromatin influences vary across related Forkhead domain TFs remains mostly uncharacterized. Here, we present a principled approach to compare the relative contributions of intrinsic DNA sequence preference and cell-specific chromatin environments to a TF’s DNA-binding activities. We over-express a selection of Fox TFs in mouse embryonic stem (mES) cells, which offer a platform to contrast each TF's binding activity within the same preexisting chromatin background. By developing and applying a neural network that jointly models sequence and chromatin data, we can evaluate how sequence and preexisting chromatin features contribute to induced TF binding, both at individual sites and genome-wide. We demonstrate that Fox TFs bind different DNA targets, and drive differential gene expression patterns, even when induced in identical chromatin settings. Differential Fox binding activities can be attributed to distinct DNA-binding preferences coupled with differential abilities to engage relatively inaccessible chromatin. We propose that varying preferences for preexisting chromatin states enables the functional diversification of paralogous TFs.
2023-10-04 | GSE244408 | GEO
Project description:Large-scale interactome screen for 89 transcription factors (TFs) in fission yeast. TFs are tagged at the endogenous locus with a 3xFLAG affinity epitope. Cells cultured under optimal conditions (30°C, rich medium) were subjected to IP-MS at 150 mM an 500 mM NaCl.
2024-08-30 | PXD054070 | Pride