Massively parallel characterization of insulator activity across the genome.

A key question in regulatory genomics is whether cis-regulatory elements (CREs) are modular elements that can function anywhere in the genome, or whether they are adapted to certain genomic locations. To distinguish between these possibilities we develop MPIRE (Massively Parallel Integrated Regulatory Elements), a technology for recurrently assaying CREs at thousands of defined locations across the genome in parallel. MPIRE allows us to separate the intrinsic activity of CREs from the effects of their genomic environments.

MeCP2 represses the activity of topoisomerase IIβ in long neuronal genes.

A unique signature of neurons is the high expression of the longest genes in the genome. These genes have essential neuronal functions, and disruption of their expression has been implicated in neurological disorders. DNA topoisomerases resolve DNA topological constraints and facilitate neuronal long gene expression.

Distinct disease mutations in DNMT3A result in a spectrum of behavioral, epigenetic, and transcriptional deficits.

Phenotypic heterogeneity in monogenic neurodevelopmental disorders can arise from differential severity of variants underlying disease, but how distinct alleles drive variable disease presentation is not well understood. Here, we investigate missense mutations in DNA methyltransferase 3A (DNMT3A), a DNA methyltransferase associated with overgrowth, intellectual disability, and autism, to uncover molecular correlates of phenotypic heterogeneity. We generate a Dnmt3a mouse mimicking a mutation with mild to moderate severity and compare phenotypic and epigenomic effects with a severe R878H mutation.

Proteomics Profiling Reveals Regulation of Immune Response to Salmonella enterica Serovar Typhimurium Infection in Mice.

Regulation of the immune response to Salmonella enterica serovar Typhimurium ( Typhimurium) infection is a complex process, influenced by the interaction between genetic and environmental factors. Different inbred strains of mice exhibit distinct levels of resistance to Typhimurium infection, ranging from susceptible (e.g.

SMAP is a pipeline for sample matching in proteogenomics.

The integration of genomics and proteomics data (proteogenomics) holds the promise of furthering the in-depth understanding of human disease. However, sample mix-up is a pervasive problem in proteogenomics because of the complexity of sample processing. Here, we present a pipeline for Sample Matching in Proteogenomics (SMAP) to verify sample identity and ensure data integrity.

Draft Genome of the Common Snapping Turtle, , a Model for Phenotypic Plasticity in Reptiles.

Turtles are iconic reptiles that inhabit a range of ecosystems from oceans to deserts and climates from the tropics to northern temperate regions. Yet, we have little understanding of the genetic adaptations that allow turtles to survive and reproduce in such diverse environments. Common snapping turtles, , are an ideal model species for studying adaptation to climate because they are widely distributed from tropical to northern temperate zones in North America.

Of snakes and succor: learning secure attachment associations with novel faces via negative stimulus pairings.

Integrating ideas from Mikulincer and Shaver's (2003) process model of attachment and Nelson and Panksepp's (1998) neurobiological theory of an integrated social emotion system, we predicted novel attachment-related learning effects. In two experiments, we tested for a unique form of conditioning based on the social regulation of emotion. Consistent with this theoretical integration, the results indicated that people develop more positive and less negative associations with faces of people who display genuine smiles if those faces have been implicitly paired with a distressing stimulus (e.