Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1156828 | ENA |
REPOSITORIES: ENA
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Project description:The MYC oncogene promoter G-quadruplex (MycG4) regulates transcription and is a prevalent G4 locus in immortal cells. Nucleolin, a major MycG4-binding protein, exhibits greater affinity for MycG4 than for nucleolin recognition element (NRE) RNA. Nucleolin's four RNA binding domains (RBDs) are essential for high-affinity MycG4 binding. We present the 2.6-angstrom crystal structure of the nucleolin-MycG4 complex, revealing a folded parallel three-tetrad G-quadruplex with two coordinating potassium ions (K+), interacting with RBD1, RBD2, and Linker12 through its 6-nucleotide (nt) central loop and 5' flanking region. RBD3 and RBD4 bind MycG4's 1-nt loops as demonstrated by nuclear magnetic resonance (NMR). Cleavage under targets and tagmentation sequencing confirmed nucleolin's binding to MycG4 in cells. Our results revealed a G4 conformation-based recognition by a regulating protein through multivalent interactions, suggesting that G4s are nucleolin's primary cellular substrates, indicating G4 epigenetic transcriptional regulation and helping G4-targeted drug discovery.
2025-05-05 | GSE276539 | GEO
Project description:The G-quadruplex is an alternative DNA structural motif that is considered to be functionally important in the mammalian genome. Herein, we address the hypothesis that G-quadruplex structures can exist within double-stranded genomic DNA using a G-quadruplex-specific probe. An engineered antibody is employed to enrich for DNA containing G-quadruplex structures, followed by deep sequencing to detect and map G-quadruplexes at high resolution in genomic DNA from human breast adenocarcinoma cells. Our high sensitivity structure-based pull-down strategy enables the isolation of genomic DNA fragments bearing a single as well as multiple G-quadruplex structures. Stable G-quadruplex structures are found in sub-telomeres, gene bodies and gene regulatory regions. For a sample of identified target genes, we show that G-quadruplex stabilizing ligands can modulate transcription. These results confirm the existence of G-quadruplex structures and their persistence in human genomic DNA. Four independent libraries have been enriched in DNA G-quadruplex structures using a G-quadruplex-specific probe. One genomic input library was sequenced as control. Deep-sequencing of these libraries allowed the mapping of G-quadruplexes on the genome.
2013-05-08 | E-GEOD-45241 | biostudies-arrayexpress
Project description:Structural basis of H2A.Z recognition and H4K20 methylation by SUV420H2
| PRJNA864759 | ENA
Project description:Structural basis of nucleosomal H4K20 recognition and methylation by SUV420H1 methyltransferase
| PRJNA989567 | ENA
Project description:The c-MYC onco-protein regulates a large array of genes playing an important role in basic cell functions. Because of its central role in growth regulation, c-MYC expression must be tightly regulated. The NHEIII1 located upstream of the P1 promoter regulates up to 80% of c-MYC transcription, and includes a C/G rich region (Pu27) which forms a G-quadruplex structure. We have identified seventeen genomic G-quadruplex-forming motifs which have more than 90% identity with Pu27 found on different chromosomes throughout the human genome. Of thirteen members of the Pu27 family tested, all interact specifically with NHEIII1 sequence and inhibit leukemic cells proliferation to differing degrees. Further characterization of three Pu27 homologous sequences (Pu5-, Pu9- and Pu27) reveals a dose/time dependent response on growth inhibition in four leukemia cell lines and down regulation of c-MYC at RNA and protein level. The three Pu27 family members selectively alter expression of genes involved in cell cycle progression/regulation, DNA damage/repair and histone modification. In conclusion, we have identified sixteen genomic G-quadruplex-forming sequences homologous to Pu27 of c-MYC promoter sharing the same structure and function. It is likely that these sequences play important biologic roles in c-MYC regulation and provide an ideal tool for targeted cancer therapy.
2017-12-01 | GSE63016 | GEO
Project description:Structural basis for the recognition of GC-motifs by Smad4 transcription factor
| PRJNA398666 | ENA
Project description:In this study we discover proteins that bind to G4 quadruplex DNA structure. We use modified c-myc quadruplex as a bait, and compare it to the control bait - T15 oligo. We use spectral counts and G-test to determine significant binders. T15 and G4 datafiles are uploaded
2016-07-07 | PXD003501 | Pride
Project description:Custom DNA microarrays reveal the selective recognition of BMVC to MYC promoter G-quadruplex: a large-scale assessment of ligand binding selectivity
| PRJNA624167 | ENA
Project description:The SWR1 chromatin remodeling complex (SRCAP in humans) is recruited to +1 nucleosomes downstream of transcription start sites of eukaryotic promoters, where it exchanges histone H2A for the specialized variant H2A.Z. Here we use cryo-EM to resolve the structural basis of the SWR1 interaction with free DNA, revealing a distinct open conformation of the Swr1 ATPase that enables sliding from accessible DNA to nucleosomes. A complete structural model of the SWR1-nucleosome complex illustrates critical structure-function roles for Swc2 and Swc3 subunits in oriented nucleosome engagement by SWR1. Moreover, an extended DNA-binding α -helix within the Swc3 subunit enables sensing of nucleosome linker length and is essential for SWR1 promoter-specific recruitment and activity. The previously unresolved N-SWR1 subcomplex forms a flexible extended structure enabling multivalent recognition of acetylated histone tails by reader domains to further direct SWR1 towards the +1 nucleosome. Altogether, our findings provide a generalizable mechanism for promoter-specific targeting of chromatin and transcription complexes.
2024-08-26 | GSE275429 | GEO