Disease variants alter transcription factor levels and methylation of their binding sites.

Most disease-associated genetic variants are noncoding, making it challenging to design experiments to understand their functional consequences. Identification of expression quantitative trait loci (eQTLs) has been a powerful approach to infer the downstream effects of disease-associated variants, but most of these variants remain unexplained. The analysis of DNA methylation, a key component of the epigenome, offers highly complementary data on the regulatory potential of genomic regions.

Identification of context-dependent expression quantitative trait loci in whole blood.

Genetic risk factors often localize to noncoding regions of the genome with unknown effects on disease etiology. Expression quantitative trait loci (eQTLs) help to explain the regulatory mechanisms underlying these genetic associations. Knowledge of the context that determines the nature and strength of eQTLs may help identify cell types relevant to pathophysiology and the regulatory networks underlying disease.

Diversity of protein-protein interactions.

In this review, we discuss the structural and functional diversity of protein-protein interactions (PPIs) based primarily on protein families for which three-dimensional structural data are available. PPIs play diverse roles in biology and differ based on the composition, affinity and whether the association is permanent or transient. In vivo, the protomer's localization, concentration and local environment can affect the interaction between protomers and are vital to control the composition and oligomeric state of protein complexes.

Structural characterisation and functional significance of transient protein-protein interactions.

Protein-protein complexes that dissociate and associate readily, often depending on the physiological condition or environment, play an important role in many biological processes. In order to characterise these "transient" protein-protein interactions, two sets of complexes were collected and analysed. The first set consists of 16 experimentally validated "weak" transient homodimers, which are known to exist as monomers and dimers at physiological concentration, with dissociation constants in the micromolar range.

Structure and dynamics of the tetrameric mnt repressor and a model for its DNA complex.

Abstract The tetrameric Mnt repressor of bacteriophage P22 consists of two dimeric DNA-binding domains and a tetramerization domain. The NOE and chemical shift data demonstrate that the structures of the domains in the wild-type repressor protein are similar to those of the separate domains, the three-dimensional structures of which have been determined previously. (15)N relaxation measurements show that the linker that connects the anti-parallel four-helix bundle with the two β-sheet DNA-binding dimers is highly flexible.