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Single-cell allelic HiC analysis, combined with allelic gene expression and chromatin states, reveals parent-of-origin-specific dynamics of chromosome organization and gene expression during mouse preimplantation development.

Paternal and maternal epigenomes undergo marked changes after fertilization(1). Recent epigenomic studies have revealed the unusual chromatin landscapes that are present in oocytes, sperm and early preimplantation embryos, including atypical patterns of histone modifications(2-4) and differences in chromosome organization and accessibility, both in gametes(5-8) and after fertilization(5,8-10). However, these studies have led to very different conclusions: the global absence of local topological-associated domains (TADs) in gametes and their appearance in the embryo(8,9) versus the pre-existence of TADs and loops in the zygote(5,11). The questions of whether parental structures can be inherited in the newly formed embryo and how these structures might relate to allele-specific gene regulation remain open. Here we map genomic interactions for each parental genome (including the X chromosome), using an optimized single-cell high-throughput chromosome conformation capture (HiC) protocol(12,13), during preimplantation in the mouse. We integrate chromosome organization with allelic expression states and chromatin marks, and reveal that higher-order chromatin structure after fertilization coincides with an allele-specific enrichment of methylation of histone H3 at lysine 27. These early parental-specific domains correlate with gene repression and participate in parentally biased gene expression-including in recently described, transiently imprinted loci(14). We also find TADs that arise in a non-parental-specific manner during a second wave of genome assembly. These de novo domains are associated with active chromatin. Finally, we obtain insights into the relationship between TADs and gene expression by investigating structural changes to the paternal X chromosome before and during X chromosome inactivation in preimplantation female embryos(15). We find that TADs are lost as genes become silenced on the paternal X chromosome but linger in regions that escape X chromosome inactivation. These findings demonstrate the complex dynamics of three-dimensional genome organization and gene expression during early development.

Colonization, speciation and extinction are dynamic processes that influence global patterns of species richness(1-6). Island biogeography theory predicts that the contribution of these processes to the accumulation of species diversity depends on the area and isolation of the island(7,8). Notably, there has been no robust global test of this prediction for islands where speciation cannot be ignored(9), because neither the appropriate data nor the analytical tools have been available. Here we address both deficiencies to reveal, for island birds, the empirical shape of the general relationships that determine how colonization, extinction and speciation rates co-vary with the area and isolation of islands. We compiled a global molecular phylogenetic dataset of birds on islands, based on the terrestrial avifaunas of 41 oceanic archipelagos worldwide (including 596 avian taxa), and applied a new analysis method to estimate the sensitivity of island-specific rates of colonization, speciation and extinction to island features (area and isolation). Our model predicts-with high explanatory power-several global relationships. We found a decline in colonization with isolation, a decline in extinction with area and an increase in speciation with area and isolation. Combining the theoretical foundations of island biogeography(7,8) with the temporal information contained in molecular phylogenies(10) proves a powerful approach to reveal the fundamental relationships that govern variation in biodiversity across the planet.

Using a global molecular phylogenetic dataset of birds on islands, the sensitivity of island-specific rates of colonization, speciation and extinction to island features (area and isolation) is estimated.