Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE242066 | GEO | 2024/08/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Genome access is transcription factor specific and defined by nucleosome position [ChIP-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 | GSE240647 | 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

BANP is an essential transcription factor that opens chromatin and activates CpG island regulated genes

Project description:While the majority of RNA polymerase II initiation events in mammalian genomes take place within CpG island (CGI) promoters, our understanding of their regulation remains limited. Here we combine single-molecule footprinting with interaction proteomics to identify BANP as a critical CGI regulator and the long sought-after TF that binds the orphan CGCG element in mouse and human. We show that BANP drives the activity of essential metabolic genes in the mouse genome in pluripotent and terminally differentiated cells. However, BANP binding is strongly repelled by DNA methylation of its motif in vitro and in vivo, which epigenetically restricts most binding to CGIs and accounts for its absence at aberrantly methylated CGIs in cancer cells. Upon binding to an unmethylated motif, BANP opens chromatin and phases nucleosomes. Our results establish Banp as a critical activator and put forth a model whereby CGI promoter activity relies on methylation-sensitive TFs capable of chromatin opening.

2021-06-16 | PXD024794 | Pride

Co-regulation of transcription factor binding and nucleosome occupancy through DNA features of mammalian enhancers

Project description:In mammalian cells transcription factors (TFs) preferentially bind sites contained in regions of high nucleosomal occupancy, as determined by nucleotide-dependent computational analysis. This observation suggests that nucleosomes may act as gatekeepers of TF binding sites. We hypothesized that in mammalian genomes the information controlling nucleosome assembly may partially coincide with the information that enables TFs to recognize cognate sites in cis-regulatory elements while ignoring the myriad of non-functional, randomly occurring consensus binding sites. This way, nucleosome-mediated masking would be coupled to TF binding site functionality. The hematopoietic master regulator Pu.1 maintained nucleosome depletion at macrophage-specific enhancers that were otherwise occupied by nucleosomes in other cell types and in reconstituted chromatin. We identified a minimal set of DNA sequence and shape features that predicted Pu.1 binding with 78% accuracy. The same features predicted nucleosome occupancy in cells where Pu.1 was not expressed with higher accuracy than specifically designed models. Control of nucleosome deposition by DNA sequence and shape features that also specify TF consensus site functionality may allow maintaining the gatekeeper function of nucleosomes during evolution of cis-regulatory elements.

2014-05-08 | GSE50762 | GEO

Basic helix-loop-helix transcription factors MYC-MAX and CLOCK-BMAL1 associate with histones for E-box access

Project description:Basic helix-loop-helix (bHLH) transcription factors (TF) recognize E-boxes (CANNTG) and include over 100 members. Here we investigated how chromatinised E-boxes are engaged by two structurally diverse bHLH family members; the proto-oncogene MYC-MAX and the circadian TF, CLOCK-BMAL1. Both bind E-boxes preferentially near the nucleosomal entry/exit sites. Structural studies with artificial or endogenous nucleosome sequences illustrate that MYC-MAX/CLOCK-BMAL1 trigger DNA release from histones to gain access. The CLOCK-BMAL1 PAS dimerization domains engage the histone-octamer disc atop the H2A/H2B acidic patch, an interaction critical for circadian cycling. Binding of tandem E-boxes at endogenous DNA sequences is similarly achieved through direct interactions between two CLOCK-BMAL1 protomers and histones. At internal E-boxes, the MYC-MAX leucine zipper can also interact with histones H2B/H3, and its binding is indirectly enhanced by OCT4 elsewhere on the nucleosome. The nucleosomal E-box position and the type of bHLH dimerisation domain jointly determine the histone contact, the affinity, and the degree of competition/cooperativity with other nucleosome-bound factors.

2023-05-23 | GSE224589 | GEO

TF co-binding to nucleosome arrays

Project description:Cell type maintenance and conversion require the combined action of transcription factors (TFs), but the underlying principles remain elusive. Here, we investigated how four TF combinations lead to different reprogramming outputs by studying TF occupancy, nucleosome positioning, and genome 3D organization. We reveal that TF combinations target nucleosome with distinct 3D nucleosome conformations. We also reveal that TFs employ different motif readout mechanisms to reach their cell type specific targets. Moreover, the ability of pioneer TFs to enable non-pioneer factors the access to closed chromatin is markedly different across combinations. Overall, our findings uncover distinct modes of action for TFs during reprogramming.

2024-09-27 | GSE201852 | GEO

High throughput screening identifies SOX2 as a Super Pioneer Factor that inhibits DNA methylation maintenance at its binding sites

Project description:Access of mammalian transcription factors (TFs) to regulatory regions, an essential event for transcription regulation, is hindered by chromatin compaction involving nucleosome wrapping, repressive histone modifications and DNA methylation. Moreover, methylation of TF binding sites (TBSs) affects TF binding affinity to these sites. Remarkably, a special class of TFs called pioneer transcription factors (PFs) can access nucleosomal DNA, leading to nucleosome remodelling and chromatin opening. However, whether PFs can bind to methylated sites and induce DNA demethylation is largely unknown. Here, we set up a highly parallelized approach to investigate PF ability to bind methylated DNA and induce demethylation. Our results indicate that the interdependence between DNA methylation and TF binding is more complex than previously thought, even within a select group of TFs that have a strong pioneering activity; while most PFs do not induce changes in DNA methylation at their binding sites, we identified PFs that can protect DNA from methylation and PFs that can induce DNA demethylation at methylated binding sites. We called the latter “super pioneer transcription factors” (SPFs), as they are seemingly able to overcome several types of repressive epigenetic marks. Importantly, while most SPFs induce TET-dependent active DNA demethylation, SOX2 binding leads to passive demethylation by inhibition of the maintenance methyltransferase DNMT1 during replication. This important finding suggests a novel mechanism allowing TFs to interfere with the epigenetic memory during DNA replication.

2021-03-18 | GSE144524 | GEO

Genome-wide maps of NME2 in A549 lung adenocarcinoma cells.

Project description:It is widely believed that reorganization of nucleosomes result in availability of transcription factor (TF) binding sites for eukaryotic gene regulation. Recent findings also show TFs induced during physiological perturbations can alter nucleosome occupancy to facilitate DNA binding. Although, these suggest a close relationship between TF binding and nucleosomes, the nature of this interaction, or to what extent it influences transcription is not clear. Moreover, since physiological perturbations induced multiple TFs, relatively direct effect of any TF on nucleosome occupancy remains poorly addressed. With these in mind, we used a single TF to induce physiological changes and following characterization of the two states (before and after induction of the TF) we determined: (a) genome wide binding sites of the TF, (b) promoter nucleosome occupancy and (c) transcriptome profiles, independently in both conditions. We find only ~20% of TF binding results from nucleosome repositioning - interestingly, almost all corresponding genes were transcriptionally altered. Whereas, when TF-occupancy was independent of nucleosome repositioning only a small fraction of corresponding genes were expressed/repressed. These observations suggest a model where TF occupancy leads to transcriptional change only when coupled with nucleosome repositioning in close proximity. This, to our knowledge, for the first time also helps explain why genome wide TF occupancy (e.g., from ChIP-sequencing) typically overlaps with only a small fraction of genes that change expression. The nature of interaction between TF binding and nucleosomes and what extent it influences transcription

2014-08-04 | E-GEOD-40300 | biostudies-arrayexpress

Pioneer factor-nucleosome binding events during differentiation are motif-encoded

Project description:Though the in vitro structural and in vivo spatial characteristics of transcription factor (TF) binding are well defined, TF interactions with chromatin and other companion TFs during development are poorly understood. To analyze such interactions in vivo, we profiled several TFs across a time course of human embryonic stem cell differentiation via CUT&RUN epigenome profiling, and studied their interactions with nucleosomes and co-occurring TFs by Enhanced Chromatin Occupancy (EChO), a computational strategy for classifying TF binding characteristics across time and space. EChO shows that at different enhancer targets, the same TF can employ either direct DNA binding, or “pioneer” nucleosome binding to access them. Pioneer binding is correlated with local binding of other TFs and enhancer motif character, including degeneracy at key bases in the pioneer factor target motif. Our strategy reveals a dynamic exchange of TFs at enhancers across developmental time that is aided by pioneer nucleosome binding.

2019-06-25 | GSE128499 | GEO

Mammalian SWI/SNF continuously restores local accessibility to chromatin [ChIP-Seq]

Project description:Open chromatin is a hallmark of regulatory regions and serves as a feature for their identification. Accessible genomic sites are mediated by the activity of transcription factors (TFs) that can engage with nucleosomes to enable stable gene expression changes that underlie development. While the variability of open chromatin between tissues has been studied in large detail, we have limited knowledge on the dynamics of accessible chromatin in any given cell. Answering this question is critical to better understand cellular memory but also to discern actual kinetics of TF binding and its consequence on local nucleosomal organization. Here we use small molecule inhibition of the catalytic subunit of the mouse SWI/SNF remodeler complex to show that accessibility at sites of TF binding critically relies on persistent activity of nucleosome remodelers. Within minutes of remodeler inhibition, accessibility decreases excluding that remodeler activity is only necessary in defined cell cycle transitions. Moreover, this surprisingly fast response is irrespective of TF function as it is similar for the pluripotency factor and activating TF Oct4 and the repressive TF Rest. Importantly, accessibility is rapidly restored upon inhibitor removal demonstrating that open chromatin is regenerated continuously and in a cell-autonomous fashion. Combined, this establishes a model where TF binding to chromatin and remodeler-mediated nucleosomal removal do not represent an initial opening event leading to a stable situation but instead open chromatin reflects an average of a highly dynamic situation that requires continued reestablishment. This argues against a model where open chromatin can persist in absence of continuous TF binding and remodeler activity.

2020-11-26 | GSE158340 | 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