Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Widespread regulatory specificities between transcriptional corepressors and enhancers in Drosophila

ABSTRACT: Animal development and homeostasis critically depend on the accurate regulation of gene expression, which includes the silencing of genes that should not be active. Silencing or repression of transcription is mediated by a specific class of transcription factors termed repressors that, typically via the recruitment of co-repressors (CoRs), can dominantly suppress transcription, even in the presence of activating cues. Here, we used functional genomics to discover previously unknown regulatory specificities between CoRs and enhancers. Enhancers can typically be repressed by only a subset of CoRs. Enhancers classified by CoR sensitivity also show distinct biological functions and endogenous chromatin features. Moreover, enhancers that are sensitive or resistant to silencing by specific CoRs differ in TF motif content. Strikingly, we identified TF motifs that are necessary and sufficient for resistance to specific CoRs, and can predict enhancer sensitivity to CoRs based on TF motif content.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE215143 | GEO | 2023/07/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Genome-wide analysis of enhancers repressed by Nkx2.2 in spinal motor neuron progenitors

Project description:Unambiguous consolidation of cell identity relies on transcription factors (TFs) acting to suppress alternative lineages, yet few general principles have emerged explaining how repressors manipulate chromatin landscapes to achieve stable gene silencing, especially in instances when these TFs are only temporarily activated. The TF Nkx2.2 is transiently expressed in CNS progenitors yet permanently abrogates somatic motor neuron (sMN) differentiation via interactions with Groucho (Grg) co-repressors. We show that Nkx2.2 inhibits regulatory elements of progenitor and postmitotic sMN transcripts by utilizing Grg to evict co-activators. Surprisingly, co-activator eviction was accomplished using Grg proteins already present at enhancers, rather than through the additional recruitment of Grg or other co-repressors. Nkx2.2-mediated enhancer silencing also led to the loss of H3K27ac modifications from H3K27me3+H3K27ac+ proximal promoters of key sMN genes, facilitating persistent repression of the sMN progenitor program after Nkx2.2 downregulation. These results imply that active loci are poised for suppression, and repressor binding mediates the transition through co-activator displacement.

2023-07-24 | GSE155229 | GEO

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

2022-12-15 | GSE211654 | GEO

Rational design of a ligand-based antagonist of jasmonate perception

Project description:The phytohormone (+)-7-iso-jasmonoyl-L-isoleucine (JA-Ile) is a major regulator of developmental and stress responses in plants. The perception of JA-Ile involves the formation of a ternary complex with the F-box protein COI1 and a member of the JAZ family of co-repressors, which leads to JAZ degradation. Coronatine (COR) is a bacterial phytotoxin that functionally mimics JA-Ile and interacts with the co-receptor COI1-JAZ complex with higher affinity than JA-Ile. Based on the crystal structure of the co-receptor, we designed ligand derivatives that spatially impede the interaction of the co-receptor proteins and, therefore, should act as competitive antagonists of COR or JA-Ile. One derivative, Coronatine O-methyloxime (COR-MO), shows a strong activity preventing COI-JAZ interaction and the subsequent JAZ degradation. COR-MO efficiently reverts the effects of JA-Ile or COR treatments on JA-mediated responses, such as anthocyanin accumulation, root-growth inhibition and gene expression in Arabidopsis plants. Moreover, it potentiates plant resistance preventing the effect of bacterially produced COR during Pseudomonas syringae infections in different plant species. In addition to the utility of COR-MO for Plant Biology research, our results underscore its biotechnological and agronomical potential for a safer and sustainable agriculture.

2014-06-20 | GSE56027 | GEO

Rational design of a ligand-based antagonist of jasmonate perception

2014-06-20 | E-GEOD-56027 | biostudies-arrayexpress

Information Content Differentiates Enhancers From Silencers in Mouse Photoreceptors

Project description:Enhancers and silencers often depend on the same transcription factors (TFs) and are imperfectly distinguished from each other by genomic assays of TF binding or chromatin state. To identify sequence features that define enhancers and silencers, we assayed massively parallel reporter libraries of genomic sequences targeted by the photoreceptor TF CRX and found instances of enhancer, silencer, or no activity. Both enhancers and silencers contain more TF motifs than inactive sequences, but enhancers contain motifs from a more diverse collection of TFs. We developed a measure of information content that describes the number and diversity of motifs in a sequence and found that, while both enhancers and silencers depend on CRX motifs, enhancers have higher information content. Our results indicate that enhancers contain motifs for a diverse but degenerate collection of TFs, while silencers depend on a smaller and less diverse collection of TFs.

2021-01-30 | GSE165812 | GEO

DeepSTARR predicts enhancer activity from DNA sequence and enables the de novo design of synthetic enhancers [Human oligo UMI-STARR-seq]

Project description:Enhancer sequences control gene expression and comprise binding sites (motifs) for different transcription factors (TFs). Despite extensive genetic and computational studies, the relationship between DNA sequence and regulatory activity is poorly understood and enhancer de novo design is considered impossible. Here we built a deep learning model, DeepSTARR, to quantitatively predict the activities of thousands of developmental and housekeeping enhancers directly from DNA sequence in Drosophila melanogaster S2 cells. The model learned relevant TF motifs and higher-order syntax rules, including functionally non-equivalent instances of the same TF motif that are determined by motif-flanking sequence and inter-motif distances. We validated these rules experimentally and demonstrated their conservation in human by testing more than 40,000 wildtype and mutant Drosophila and human enhancers. Finally, we designed and functionally validated synthetic enhancers with desired activities de novo.

2022-02-24 | GSE183938 | GEO

DeepSTARR predicts enhancer activity from DNA sequence and enables the de novo design of synthetic enhancers [Drosophila oligo UMI-STARR-seq]

2022-02-24 | GSE183937 | GEO

DeepSTARR predicts enhancer activity from DNA sequence and enables the de novo design of synthetic enhancers [Drosophila genome-wide UMI-STARR-seq]

2022-02-24 | GSE183936 | GEO