second model, the two main conditions were parametrically modulated by the two categories, respectively (SOM, S5.1). The activation of the precuneus was higher for hard dominance-solvable games than for easy ones ( Fig. 4A and table S10). The activation of the insula was higher for the highly focal coordination games than for less focal ones ( Fig. 4B and table S11). Previous studies also found that precuneus activity increased when the number of planned moves increased (40, 41). The higher demand for memory-related imagery and memory retrieval may explain the greater precuneus activation in hard dominance-solvable games. In highly focal coordination games, the participants may have felt quite strongly that the pool students must notice the same salient feature. This may explain why insula activation correlates with NCI.Participants might have disagreed about which games were difficult. We built a third model to investigate whether the frontoparietal activation correlates with how hard a dominance-solvable game is and whether the activation in insula and ACC correlates with how easy a coordination game is. Here, the two main conditions were parametrically modulated by each participant's probability of obtaining a reward in each game (SOM, S2.2 and S5.2). We found a negative correlation between the activation of the precuneus and the participant's probability of obtaining a reward in dominance-solvable games ( Fig. 4C and table S12), which suggests that dominance-solvable games that yielded lower payoffs presented harder mental challenges. In a previous study on working memory, precuneus activity positively correlated with response times, a measure of mental effort (24). Both findings are consistent with the interpretation that subjective measures reflecting harder tasks (higher efforts) correlate with activation in precuneus. A positive correlation between insula activation and the participant's probability of obtaining a reward again suggests that coordination games with a highly salient feature strongly activated the "gut feeling" reported by many participants (Fig. 4D and table S13). A previous study found that the subjective rating of "chills intensity" in music correlates with activation of insula (42). Both findings are consistent with the interpretation that the subjective intensity of how salient a stimulus is correlates with activation in insula.As mentioned, choices were made significantly faster in coordination games than in dominancesolvable games. The results of the second and third models provide additional support for the idea that intuitive and deliberative mental processes have quite different properties. The "slow and effortful" process was more heavily taxed when the dominance-solvable games were harder. The "fast and effortless" process was more strongly activated when coordination was easy.

The ability to correlate chromosome conformation and gene expression gives a great deal of information regarding the strategies used by a cell to properly regulate gene activity. 4C-Seq is a relatively new and increasingly popular technology where the set of genomic interactions generated by a single point in the genome can be determined. 4C-Seq experiments generate large, complicated data sets and it is imperative that signal is properly distinguished from noise. Currently, there are a limited number of methods for analyzing 4C-Seq data. Here, we present a new method, fourSig, which in addition to being precise and simple to use also includes a new feature that prioritizes detected interactions. Our results demonstrate the efficacy of fourSig with previously published and novel 4C-Seq data sets and show that our significance prioritization correlates with the ability to reproducibly detect interactions among replicates.

X chromosome inactivation (XCI) is an epigenetic process that almost completely inactivates one of two X chromosomes in somatic cells of mammalian females. A few genes are known to escape XCI and the mechanism for this escape remains unclear. Here, using mouse trophoblast stem (TS) cells, we address whether particular chromosomal interactions facilitate escape from imprinted XCI. We demonstrate that promoters of genes escaping XCI do not congregate to any particular region of the genome in TS cells. Further, the escape status of a gene was uncorrelated with the types of genomic features and gene activity located in contacted regions. Our results suggest that genes escaping imprinted XCI do so by using the same regulatory sequences as their expressed alleles on the active X chromosome. We suggest a model where regulatory control of escape from imprinted XCI is mediated by genomic elements located in close linear proximity to escaping genes.T HE three-dimensional shape of chromosomes has a direct impact upon gene regulation, as chromatin looping mediates the interaction of enhancers with transcriptional start sites (TSSs) (Lieberman-Aiden et al. 2009;Li and Reinberg 2011;Krivega and Dean 2012). Analysis of genome-wide interactions suggests that chromosomes self-organize into topologically associated domains (TADs) that are 0.8-1 Mb in linear length (Dixon et al. 2012). Loci within a TAD are more likely to interact with each other as opposed to forming interactions with loci residing in other TADs.Chromosomal interactions are thought to play a pivotal role in the epigenetic process of X chromosome inactivation (XCI) (Splinter et al. 2011). During XCI, mammalian females transcriptionally inactivate one X chromosome (Xi) per somatic cell to balance X-linked gene dosage with males (Chow and Heard 2009). Whereas genes on the active X chromosome (Xa) are thought to form stable interactions with other loci on the Xa (cis) and other chromosomes (trans), the interactions formed by Xi-linked loci are relatively less established, suggesting that Xi chromatin folds in a random manner (Splinter et al. 2011).In the mouse, two forms of XCI are observed: imprinted XCI and random XCI. Imprinted XCI occurs within extra-embryonic tissues and is characterized by the exclusive inactivation of the paternally derived X chromosome (Xp) (Takagi and Sasaki 1975). Random XCI occurs within somatic tissues of the developing embryo and adult (Lyon 1961). While imprinted and random XCI may initiate via distinct mechanisms (Kalantry et al. 2009), the genetic programs required for the maintenance of both forms appear similar (Marahrens et al. 1997;Kalantry et al. 2006;Jonkers et al. 2009; Shin et al. 2010).Interestingly, a few genes are known to escape both imprinted and random XCI and are expressed from both X chromosomes (Berletch et al. 2011;. Profiles of XCI escape vary among different cell types; the number of escape genes, termed escapers, ranges from 3% to 25% of all X-linked genes (Berletch et al. 2011 To date, no study has c...

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