Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Electrostatic properties of disordered regions control transcription factor search and pioneer activity [ChIP-Seq]

ABSTRACT: Transcription factors (TFs) recognize specific target sites within cis-regulatory regions to control gene expression. Prokaryotic TFs combine 1D and 3D diffusion mechanisms to efficiently locate their binding sites. In contrast, the determinants of target search efficiency of eukaryotic TFs within the chromatinized genome are poorly characterized. Here we combine in vivo and in vitro single molecule imaging to dissect the role of charged disordered regions of the mammalian Sox2 and Sox17 TFs in their ability to search for their binding sites. We demonstrate that the DBD flanking region of Sox2 (DFRSox2) dramatically enhances Sox2 search efficiency as compared to the negatively-charged DFRSox17 through distinct mechanisms on naked versus nucleosomal DNA. Enhanced search on naked DNA is primarily mediated by an increase in target recognition rate during 1D sliding. In contrast, target site recognition within nucleosomal DNA is mainly enhanced by increased nonspecific interactions with nucleosomes, facilitating binding to closed chromatin and reinforcing pioneering activity. These findings provide critical insights into the biophysical mechanisms governing TF target search beyond the DBD, and demonstrate how charged disordered regions modulate TF target search on the chromatinized genome.

ORGANISM(S): Mus musculus

PROVIDER: GSE290874 | GEO | 2025/04/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Electrostatic properties of disordered regions control transcription factor search and pioneer activity [ATAC-Seq]

Project description:Transcription factors (TFs) recognize specific target sites within cis-regulatory regions to control gene expression. Prokaryotic TFs combine 1D and 3D diffusion mechanisms to efficiently locate their binding sites. In contrast, the determinants of target search efficiency of eukaryotic TFs within the chromatinized genome are poorly characterized. Here we combine in vivo and in vitro single molecule imaging to dissect the role of charged disordered regions of the mammalian Sox2 and Sox17 TFs in their ability to search for their binding sites. We demonstrate that the DBD flanking region of Sox2 (DFRSox2) dramatically enhances Sox2 search efficiency as compared to the negatively-charged DFRSox17 through distinct mechanisms on naked versus nucleosomal DNA. Enhanced search on naked DNA is primarily mediated by an increase in target recognition rate during 1D sliding. In contrast, target site recognition within nucleosomal DNA is mainly enhanced by increased nonspecific interactions with nucleosomes, facilitating binding to closed chromatin and reinforcing pioneering activity. These findings provide critical insights into the biophysical mechanisms governing TF target search beyond the DBD, and demonstrate how charged disordered regions modulate TF target search on the chromatinized genome.

2025-04-02 | GSE290873 | GEO

FoxP3 Pulldown-seq (Nucleosomal DNA)

Project description:To investigate the interactions between FoxP3 and chromatinized templates, particularly assessing whether FoxP3 can still bind significantly to TnG-repeat DNA, we conducted FoxP3 pulldown experiments using nucleosomal DNA. Consitent with the result using naked genomic DNA, the results highlighted TnG repeats as one of the most significant motifs in these interactions.

2023-10-09 | GSE243605 | GEO

Genome access is transcription factor specific and defined by nucleosome position [NOMe-seq]

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

Genome access is transcription factor specific and defined by nucleosome position [ChIP-Seq]

2024-08-13 | GSE240647 | GEO

GHT-SELEX demonstrates unexpectedly high intrinsic sequence specificity of many human transcription factors

Project description:A long-standing challenge in human regulatory genomics is that transcription factor (TF) DNA-binding motifs are short and degenerate, while the genome is large. Motif scans therefore produce many false-positive binding site predictions. By surveying TFs across 25 families using >1,500 cyclic in vitro selection experiments with fragmented, naked, and unmodified genomic DNA – a method we term GHT-SELEX (Genomic HT-SELEX) – we find that many human TFs possess much higher sequence specificity than anticipated. Moreover, genomic binding regions from GHT-SELEX are often surprisingly similar to those obtained in vivo (i.e. ChIP-seq peaks). We find that comparable specificity can also be obtained from motif scans, but performance is highly dependent on derivation and use of the motifs, including accounting for multiple local matches in the scans. We also observe alternative engagement of multiple DNA-binding domains within the same protein: long C2H2 zinc finger proteins often utilize modular DNA recognition, engaging different subsets of their DNA binding domain (DBD) arrays to recognize multiple types of distinct target sites, frequently evolving via internal duplication and divergence of one or more DBDs. Thus, contrary to conventional wisdom, it is common for TFs to possess sufficient intrinsic specificity to independently delineate cellular targets.

2024-11-11 | GSE278858 | GEO

Nucleosome mapping in Saccharomyces cerevisiae in different conditions

Project description:This experiment aims to map nucleosome positions and comparison of the same in WT NORMAL GROWTH vs WT-NUTRIENT STARVATION/isw1∆2∆ MUTANT/rsc4-∆4 MUTANT in Saccharomyces cerevisiae using a custom designed tiling array on Agilent plat form. The corresponding platform is submitted to GEO under Geo-ID GPL15842. 60mer probes with variable tiling density were designed for all the genes transcribed by RNA polymerase III. Each gene is tiled along with its 1kb downstream and upstream region with the exceptions of RPR1, SCR1, RDN5(1-6) and SNR52. Mononucleosomal DNA and size matched naked DNA was competitively hybridized to the array. Data was extracted and normalized log ratios were calculated using Agilent sofware. Normalized log2 ratio data was used in MLM to detection nucleosome positions. Equal amount of mono-nucleosomal DNA and sized matched naked DNA prepared from formaldehyde fixed cells (Yuan et al. 2005), was labeled with Cy5 and Cy3 respectively and hybridized to the microarray. Each Hybridization was done in triplicate from three independent biological samples in each condition. Enrichment of mono-nucleosomal DNA over naked genomic DNA is a measure of nucleosome density calculated as Log2(nucDNA/nakedDNA).

2013-06-21 | E-GEOD-39802 | biostudies-arrayexpress

Heat shock transcription factors demonstrate a distinct mode of interaction with mitotic chromosomes

Project description:A large number of transcription factors have been shown to bind and interact with mitotic chromosomes, which may promote the efficient reactivation of transcriptional programs following cell division. Although the DNA-binding domain (DBD) contributes strongly to TF behavior, the mitotic behaviors of TFs from the same DBD family may vary. To define the mechanisms governing TF behavior during mitosis in mouse embryonic stem cells, we examined two related TFs: Heat Shock Factor 1 and 2 (HSF1 and HSF2). We found that HSF2 maintains site-specific binding genome-wide during mitosis, whereas HSF1 binding is somewhat decreased. Surprisingly, live-cell imaging shows that both factors appear excluded from mitotic chromosomes to the same degree, and are similarly more dynamic in mitosis than in interphase. Exclusion from mitotic DNA is not due to extrinsic factors like nuclear import and export mechanisms. Rather, we found that the HSF DBDs can coat mitotic chromosomes, and that HSF2 DBD is able to establish site-specific binding. These data further confirm that site-specific binding and chromosome coating are independent properties, and that for some TFs, mitotic behavior is largely determined by the non-DBD regions.

2023-04-28 | GSE214219 | GEO

CTCF confers local nucleosome resiliency after DNA replication and during mitosis

Project description:The access of Transcription Factors (TFs) to their cognate DNA binding motifs requires a precise control over nucleosome positioning. This is especially important following DNA replication and during mitosis, both resulting in profound changes in nucleosome organization over TF binding regions. Using mouse Embryonic Stem (ES) cells, we show that the TF CTCF displaces nucleosomes from its binding site and locally organizes large and phased nucleosomal arrays, not only in interphase steady-state but also immediately after replication and during mitosis. While regions bound by other TFs, such as Oct4 and Sox2, display major rearrangement, the post-replication and mitotic nucleosome organization activity of CTCF is not likely to be unique: Esrrb binding regions are also characterized by persistent nucleosome positioning. Therefore, selected TFs such as CTCF and Esrrb act as resilient TFs governing the inheritance of nucleosome positioning at gene regulatory regions throughout the ES cell-cycle.

2019-11-05 | GSE131356 | GEO

Principal components of embryonic stem cell pluripotency

Project description:To decipher gene regulatory networks, we used systematic suppression of 97 transcription factors (TFs) and 7 other genes with shRNA in mouse embryonic stem (ES) cells, followed by global gene expression profiling. Meta-analysis of these data together with the earlier data obtained by the induction of 50 TFs and the existing genome-wide data on TF binding sites identified the sets of regulated target genes for 23 TFs. Principal component analysis shows different roles of two groups of TFs that are active in ES cells: Pou5f1 and Sox2 support the expression of their target genes and prevent the upregulation of trophectoderm-related genes, whereas Esrrb, Sall4, Nanog, Gbx2, Grhl2, Mtf2, Aff1, Tcfap4, and Cdc5l support the expression of targets of Esrrb, including glycolysis genes, and prevent upregulation of targets of Trp53 and Polycomb TFs. If TFs from the second group are downregulated while Pou5f1 and Sox2 are still active, then the cell state changes towards epiblast lineages.

2013-03-14 | GSE26520 | GEO

Distinct Chromatin Scanning Modes Lead to Targeting of Compacted Chromatin by Pioneer Factors FOXA1 and SOX2 [Cut&Run]

Project description:Pioneer transcription factors, by interacting with nucleosomes, scan silent, compact chromatin to target regulatory sequences, enabling cooperative binding events that modulate local chromatin structure and gene activity. However, not all cognate motifs are targeted by pioneer factors and dynamic scanning parameters required to scan compact chromatin are unknown. A combined genomics and single-molecule tracking approach shows that to target DNase-resistant, low-histone turnover sites, pioneer factors FOXA1 and SOX2 display opposite dynamics of chromatin scanning: slow, with low nucleoplasmic diffusion and stable interactions, versus fast, with high nucleoplasmic diffusion and transient interactions, respectively. Despite such differences, the ability of FOXA1 and SOX2 to scan low-mobility chromatin, mediated by protein domains outside of the respective DNA binding domains, leads to targeting silent chromatin. By contrast, non-pioneer HNF4A predominantly targets DNase-sensitive, nucleosome-depleted regions. We conclude that the targeting of compact chromatin sites by pioneer factors can be performed through diverse dynamic processes. Cleavage under Targets and Release Using Nuclease (CUT&RUN) of SOX2 and SOX2-DBD after ectopic expression in BJ fibroblasts.

2023-06-07 | GSE220568 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data