相关论文: Long-term evolution of regulatory DNA sequences. P…
Promoters and enhancers are cis-regulatory elements (CREs), DNA sequences that bind transcription factor (TF) proteins to up- or down-regulate target genes. Decades-long efforts yielded TF-DNA interaction models that predict how strongly an…
Cis-regulatory elements (CREs), such as promoters and enhancers, are relatively short DNA sequences that directly regulate gene expression. The fitness of CREs, measured by their ability to modulate gene expression, highly depends on the…
Regulatory networks consist of interacting molecules with a high degree of mutual chemical specificity. How can these molecules evolve when their function depends on maintenance of interactions with cognate partners and simultaneous…
Predicting how genetic variation affects phenotypic outcomes at the organismal, cellular, and molecular levels requires deciphering the cis-regulatory code, the sequence rules by which non-coding regions regulate genes. In this perspective,…
The two most fundamental processes describing change in biology, development and evolu-tion, occur over drastically different timescales, difficult to reconcile within a unified framework. Development involves temporal sequences of cell…
Evolution of gene regulation is crucial for our understanding of the phenotypic differences between species, populations and individuals. Sequence-specific binding of transcription factors to the regulatory regions on the DNA is a key…
Gene Regulatory Networks (GRNs) consisting of combinations of transcription factors (TFs) and their cis promoters are assumed to be sufficient to direct the development of organisms. Mutations in GRNs are assumed to be the primary drivers…
Multi-sample microarray experiments have become a standard experimental method for studying biological systems. A frequent goal in such studies is to unravel the regulatory relationships between genes. During the last few years, regression…
Gene regulation is a complex process involving the role of several genomic elements which work in concert to drive spatio-temporal expression. The experimental characterization of gene regulatory elements is a very complex and…
Gene expression is a central process to any form of life. It involves multiple temporal and functional scales that extend from specific protein-DNA interactions to the coordinated regulation of multiple genes in response to intracellular…
Genetic variation affecting gene regulation is a central driver of phenotypic differences between individuals and can be used to uncover how biological processes are organized in a cell. Although detecting cis-eQTLs is now routine,…
Transcriptional regulation of gene expression is one of the main processes that affect cell diversification from a single set of genes. Regulatory proteins often interact with DNA regions located distally from the transcription start sites…
The evolutionary origins of structural features in reconstructed gene-regulatory networks (GRNs) remain poorly understood, especially given the random aspects of gene expression. Here, we extend a classical model of GRN evolution to allow a…
Identity, response to external stimuli, and spatial architecture of a living system are central topics of molecular biology. Presently, they are largely seen as a result of the interplay between a gene repertoire and the regulatory…
Predicting genetic perturbations enables the identification of potentially crucial genes prior to wet-lab experiments, significantly improving overall experimental efficiency. Since genes are the foundation of cellular life, building gene…
The prevalence of neutral mutations implies that biological systems typically have many more genotypes than phenotypes. But can the way that genotypes are distributed over phenotypes determine evolutionary outcomes? Answering such questions…
Designing regulatory DNA sequences that achieve precise cell-type-specific gene expression is crucial for advancements in synthetic biology, gene therapy and precision medicine. Although transformer-based language models (LMs) can…
The mutation and selection of regulatory DNA sequences is presented as an ideal model system of molecular evolution where genotype, phenotype, and fitness can be explicitly and independently characterized. In this theoretical study, we…
Gene regulatory networks (GRNs) define the regulatory relationships among molecules such as transcription factors, chromatin remodelers, and target genes. GRNs play a critical role in diverse biological processes, including development,…
Turnover of regulatory sequence and function is an important part of molecular evolution. But what are the modes of sequence evolution leading to rapid formation and loss of regulatory sites? Here, we show that a large fraction of…