Leonid A. Mirny

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We describe Hi-C, a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. We constructed spatial proximity maps of the human genome with Hi-C at a resolution of 1 megabase. These maps confirm the presence of chromosome territories and the spatial proximity of small,(More)
Proteins, nucleic acids, and small molecules form a dense network of molecular interactions in a cell. Molecules are nodes of this network, and the interactions between them are edges. The architecture of molecular networks can reveal important principles of cellular organization and function, similarly to the way that protein structure tells us about the(More)
Extracting biologically meaningful information from chromosomal interactions obtained with genome-wide chromosome conformation capture (3C) analyses requires the elimination of systematic biases. We present a computational pipeline that integrates a strategy to map sequencing reads with a data-driven method for iterative correction of biases, yielding(More)
Here, we provide an analysis of molecular evolution of five of the most populated protein folds: immunoglobulin fold, oligonucleotide-binding fold, Rossman fold, alpha/beta plait, and TIM barrels. In order to distinguish between "historic", functional and structural reasons for amino acid conservations, we consider proteins that acquire the same fold and(More)
Recognition and binding of specific sites on DNA by proteins is central for many cellular functions such as transcription, replication, and recombination. In the process of recognition, a protein rapidly searches for its specific site on a long DNA molecule and then strongly binds this site. Here we aim to find a mechanism that can provide both a fast(More)
Cooperative binding of transcription factors (TFs) to promoters and other regulatory regions is essential for precise gene expression. The classical model of cooperativity requires direct interactions between TFs, thus constraining the arrangement of TF sites in regulatory regions. Recent genomic and functional studies, however, demonstrate a great deal of(More)
In this paper we introduce a novel method of deriving a pairwise potential for protein folding. The potential is obtained by an optimization procedure that simultaneously maximizes thermodynamic stability for all proteins in the database. When applied to the representative dataset of proteins and with the energy function taken in pairwise contact(More)
Topologically associating domains (TADs) are fundamental structural and functional building blocks of human interphase chromosomes, yet the mechanisms of TAD formation remain unclear. Here, we propose that loop extrusion underlies TAD formation. In this process, cis-acting loop-extruding factors, likely cohesins, form progressively larger loops but stall at(More)
Coordinated regulation of gene expression relies on transcription factors (TFs) binding to specific DNA sites. Our large-scale information-theoretical analysis of > 950 TF-binding motifs demonstrates that prokaryotes and eukaryotes use strikingly different strategies to target TFs to specific genome locations. Although bacterial TFs can recognize a specific(More)