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Results for “SELEX”

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PubMed2026

GHT-SELEX demonstrates unexpectedly high intrinsic sequence specificity and complex DNA binding of many human transcription factors.

There is ongoing debate regarding the degree to which transcription factors (TFs) independently specify genomic binding: TF binding motifs are typically short and degenerate, yielding many more binding site predictions than observed in cells. Here we present genomic high-throughput SELEX (GHT-SELEX)-a scalable method that surveys intrinsic binding of purified TFs to the fragmented, naked and unmodified genome. GHT-SELEX peaks for 179 diverse human TFs display surprisingly high overlap with chromatin immunoprecipitation sequencing peaks for the same TF. Comparable overlap can be obtained from motifs using appropriate analytical approaches. For C2H2 zinc finger (zf) proteins-the largest class of human TFs-GHT-SELEX shows that modular, alternative engagement of C2H2-zf domains is the norm, enabling several types of distinct target sites, and frequently involving internal duplication and divergence within the C2H2-zf array. Altogether, it is common for TFs to delineate a large fraction of in vivo genomic binding sites independently of other cellular factors.

Humans↗

PubMed2024

GHT-SELEX demonstrates unexpectedly high intrinsic sequence specificity and complex DNA binding of many human transcription factors.

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 179 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.

C2H2↗

PubMed1992

Selection of high affinity RNA ligands to the bacteriophage R17 coat protein.

RNA ligands with high affinity for the bacteriophage R17 coat protein were isolated from a pool of random RNA molecules using SELEX. Of the 38 ligands isolated, 36 were found to contain a hairpin very similar to the naturally occurring coat protein binding site in the R17 genome. The common features of these 36 sequences provide a consensus binding site and predict components of a hairpin that promote favorable interaction with the coat protein. These include a tetraloop of primary sequence AUCA and a variable-length stem with a bulged adenosine residue at a specific stem position. The predicted consensus agrees well with the highest-affinity RNA binding site of the R17 coat protein, identified through classical but laborious techniques. These results demonstrate the value of SELEX as a tool for isolating high affinity RNA ligands to a specific target protein, and the further value of those ligands to point the researcher toward natural sequences for that target protein.

Allosteric Regulation↗

PubMed1992

RNA pseudoknots that inhibit human immunodeficiency virus type 1 reverse transcriptase.

High-affinity ligands of the reverse transcriptase of human immunodeficiency virus type 1 (HIV-1) were isolated by the SELEX procedure (systematic evolution of ligands by exponential enrichment) from RNA populations randomized at 32 positions. Analysis of these ligands revealed a pseudoknot consensus with primary sequence bias at some positions. We demonstrated that at least one of the ligands inhibits cDNA synthesis by HIV reverse transcriptase but fails to inhibit other reverse transcriptases. These experiments highlight the power of SELEX to yield highly specific ligands that reduce the activity of target proteins. Such ligands may provide therapeutic reagents for viral and other diseases.

Antiviral Agents↗

PubMed2026

Aptamer-Based Platforms for Human Aging Biomarkers: Multiplexed Proteomics, Biosensors and Translational Perspectives.

Aptamer-based multiplexed proteomic platforms, especially the SOMAmer-based SomaScan assay, are widely used for large-scale discovery of circulating biomarkers relevant to human aging. This review summarizes 42 original research articles published from 2020 through 2026 in which aptamers or aptamer-derived biosensors were used to characterize aging-related biomarkers in human samples or clinically relevant human-disease contexts. The eligible literature falls into several thematic areas: whole-plasma and organ-specific proteomic aging clocks; inflammaging and senescence-associated secretory phenotype (SASP) markers; cardiovascular, metabolic, renal, hepatic, musculoskeletal and neurodegenerative biomarker panels; and aptasensor platforms for detection of individual analytes. Only a small number of studies have compared aptamer- and antibody-based platforms in the same specimens; we tabulate these and show that median between-platform agreement is low to moderate, which constrains the pooling of findings across technologies. We also make explicit an interpretive point that is usually left implicit: because proteomic clocks are trained against chronological age, their correlation with chronological age measures fit to the training target rather than biological validity, and the informative quantity is the residual age gap. In the reviewed literature, SomaScan-based studies are concentrated in cardiovascular, neurodegenerative, frailty, and proteomic aging-clock research, whereas de novo SELEX campaigns targeting aging-specific epitopes and longitudinal human validation of wearable aptasensors were not identified. The main barriers to translation are cross-platform discordance, limited replication across ancestries, under-reported pre-analytical variability, cost, and the research-use-only status of most assays.

Humans↗

PubMed2026

Decoding sequence recognition code of nucleic acid-binding proteins of human-infecting DNA viruses.

Human-infecting DNA viruses remain major health threats, yet the DNA-recognition mechanisms of their nucleic acid-binding proteins (NBPs) are poorly understood. Here, we systematically profiled 103 viral NBPs from human-infecting DNA viruses, with three NBPs from non-human-infecting DNA viruses as controls, using high-throughput screening. This analysis identified diverse DNA-binding motifs and specificity modules, including convergent recognition of a conserved CCACC motif across phylogenetically distant viruses. Notably, viral NBP binding-site distributions varied with genome size, and several NBPs from small-genome viruses showed enrichment on mitochondrial DNA. Functional assays further supported their mitochondrial association and effects on mitochondrial membrane potential. By integrating an ivTRT-based ssDNA-SELEX workflow, we further found that ssDNA viral NBPs recognize dimer-like and inverted-repeat sequences with potential to form stem-loop structures. Collectively, this study constructs a comprehensive viral NBP DNA-recognition atlas, offering a fundamental resource for elucidating viral genome recognition mechanisms, virus-mitochondria interactions, and developing future antiviral strategies.

Letter↗

PubMed1992

In vitro evolution of intrinsically bent DNA.

DNA fragments which are intrinsically bent or curved migrate anomalously during electrophoresis through polyacrylamide gels. Starting with an initial population of approximately 10(12) unique DNA sequences, DNA which exhibited the kind of anomalous mobility associated with DNA bending was selected and enriched using a variation of the SELEX procedure. After seven rounds of selection and amplification, the vast majority of the remaining population of DNA fragments migrated as bent DNA. Cloning and sequencing of 30 individual sequences from this population has yielded information regarding the relationship between DNA sequence and bending. Some of the previous conclusions on DNA bending have been confirmed while others have been modified, by the results presented here. In addition, the dinucleotide base step CA/TG, which had not been thought to be a major factor in DNA bending, appears to be important.

Base Composition↗