Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Enhancers display sequence flexibility constrained by transcription factor motif syntax

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens Drosophila melanogaster

PROVIDER: GSE211659 | GEO | 2022/12/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Enhancers display sequence flexibility constrained by transcription factor motif syntax [Drosophila motif pasting STARR-seq]

Project description:The information about when and where each gene is to be expressed is mainly encoded in the DNA sequence of enhancers, sequence elements that comprise binding sites (motifs) for different transcription factors (TFs). Most of the research on enhancer sequences has been focused on TF motif presence, while the enhancer syntax, i.e. the flexibility of important motif positions and how the sequence context modulates the activity of TF motifs, remain poorly understood. Here, we explore the rules of enhancer syntax by a two-pronged approach in Drosophila melanogaster S2 cells: we (1) replace important motifs by an exhaustive set of all possible 65,536 eight-nucleotide-long random sequences and (2) paste eight important TF motif types into 763 motif positions within 496 enhancers. These complementary strategies reveal that enhancers display constrained sequence flexibility and the context-specific modulation of motif function. Important motifs can be functionally replaced by hundreds of sequences constituting several distinct motif types, but only a fraction of all possible sequences and motif types restore enhancer activity. Moreover, TF motifs contribute with different intrinsic strengths that are strongly modulated by the enhancer sequence context (the flanking sequence, presence and diversity of other motif types, and distance between motifs), such that not all motif types can work in all positions. Constrained sequence flexibility and the context-specific modulation of motif function are also hallmarks of human enhancers and TF motifs, as we demonstrate experimentally. Overall, these two general principles of enhancer sequences are important to understand and predict enhancer function during development, evolution and in disease.

2022-12-15 | GSE211654 | GEO

Enhancers display sequence flexibility constrained by transcription factor motif syntax [Human motif pasting STARR-seq]

2022-12-15 | GSE211657 | GEO

Enhancers display sequence flexibility constrained by transcription factor motif syntax [Drosophila random variant STARR-seq]

2022-12-15 | GSE211655 | GEO

Enhancers display sequence flexibility constrained by transcription factor motif syntax

Project description:Enhancers display sequence flexibility constrained by transcription factor motif syntax

| PRJNA871261 | ENA

Enhancers display sequence flexibility constrained by transcription factor motif syntax [Human motif pasting STARR-seq]

Project description:Enhancers display sequence flexibility constrained by transcription factor motif syntax [Human motif pasting STARR-seq]

| PRJNA871264 | ENA

Enhancers display sequence flexibility constrained by transcription factor motif syntax [Drosophila motif pasting STARR-seq]

Project description:Enhancers display sequence flexibility constrained by transcription factor motif syntax [Drosophila motif pasting STARR-seq]

| PRJNA871262 | ENA

Enhancers display sequence flexibility constrained by transcription factor motif syntax [Drosophila random variant STARR-seq]

Project description:Enhancers display sequence flexibility constrained by transcription factor motif syntax [Drosophila random variant STARR-seq]

| PRJNA871263 | ENA

Constrained Peptides with Fine-Tuned Flexibility Inhibit NF-Y Transcription Factor Assembly.

Project description:Protein complex formation depends on the interplay between preorganization and flexibility of the binding epitopes involved. The design of epitope mimetics typically focuses on stabilizing a particular bioactive conformation, often without considering conformational dynamics, which limits the potential of peptidomimetics against challenging targets such as transcription factors. We developed a peptide-derived inhibitor of the NF-Y transcription factor by first constraining the conformation of an epitope through hydrocarbon stapling and then fine-tuning its flexibility. In the initial set of constrained peptides, a single non-interacting α-methyl group was observed to have a detrimental effect on complex stability. Biophysical characterization revealed how this methyl group affects the conformation of the peptide in its bound state. Adaption of the methylation pattern resulted in a peptide that inhibits transcription factor assembly and subsequent recruitment to the target DNA.

| S-EPMC6900064 | biostudies-literature

Transcription factor stoichiometry, motif affinity and syntax regulate single-cell chromatin dynamics during fibroblast reprogramming to pluripotency

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-09-06 | GSE242424 | GEO

Transcription factor stoichiometry, motif affinity and syntax regulate single-cell chromatin dynamics during fibroblast reprogramming to pluripotency.

Project description:Ectopic expression of OCT4, SOX2, KLF4 and MYC (OSKM) transforms differentiated cells into induced pluripotent stem cells. To refine our mechanistic understanding of reprogramming, especially during the early stages, we profiled chromatin accessibility and gene expression at single-cell resolution across a densely sampled time course of human fibroblast reprogramming. Using neural networks that map DNA sequence to ATAC-seq profiles at base-resolution, we annotated cell-state-specific predictive transcription factor (TF) motif syntax in regulatory elements, inferred affinity- and concentration-dependent dynamics of Tn5-bias corrected TF footprints, linked peaks to putative target genes, and elucidated rewiring of TF-to-gene cis-regulatory networks. Our models reveal that early in reprogramming, OSK, at supraphysiological concentrations, rapidly open transient regulatory elements by occupying non-canonical low-affinity binding sites. As OSK concentration falls, the accessibility of these transient elements decays as a function of motif affinity. We find that these OSK-dependent transient elements sequester the somatic TF AP-1. This redistribution is strongly associated with the silencing of fibroblast-specific genes within individual nuclei. Together, our integrated single-cell resource and models reveal insights into the cis-regulatory code of reprogramming at unprecedented resolution, connect TF stoichiometry and motif syntax to diversification of cell fate trajectories, and provide new perspectives on the dynamics and role of transient regulatory elements in somatic silencing.

| S-EPMC10592962 | biostudies-literature

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