Single-molecule footprinting identifies context-dependent regulation of enhancers by DNA methylation.

Enhancers are cis-regulatory elements that control the establishment of cell identities during development. In mammals, enhancer activation is tightly coupled with DNA demethylation. However, whether this epigenetic remodeling is necessary for enhancer activation is unknown. Here, we adapted single-molecule footprinting to measure chromatin accessibility and transcription factor binding as a function of the presence of methylation on the same DNA molecules. We leveraged natural epigenetic heterogeneity at active enhancers to test the impact of DNA methylation on their chromatin accessibility in multiple cell lineages. Although reduction of DNA methylation appears dispensable for the activity of most enhancers, we identify a class of cell-type-specific enhancers where DNA methylation antagonizes the binding of transcription factors. Genetic perturbations reveal that chromatin accessibility and transcription factor binding require active demethylation at these loci. Thus, in addition to safeguarding the genome from spurious activation, DNA methylation directly controls transcription factor occupancy at active enhancers.

Dermatoglyphics, handedness, sex, and sexual orientation.

Both handedness and dermatoglyphic asymmetry reflect early, prenatal influences and both have been reported to be associated with male sexual orientation; handedness has been related to female sexual orientation as well. Neurohormonal and developmental perturbation are two competing hypothesis that attempt to explain these connections. We attempted to replicate these associations and to extend dermatoglyphic asymmetry findings to women. Dermatoglyphic directional asymmetry and fluctuating asymmetry were unrelated to sexual orientation. Homosexual women, but not homosexual men, had highly significant increases in non-right-handedness compared with same-sex heterosexual controls. Although this pattern of results does not allow resolution of the two competing models, it does lend additional support to a biological basis of sexual orientation.