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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.

Tandem repeat elements such as the diverse class of satellite repeats occupy large parts of eukaryotic chromosomes, mostly at centromeric, pericentromeric, telomeric and subtelomeric regions(1). However, some elements are located in euchromatic regions throughout the genome and have been hypothesized to regulate gene expression in cis by modulating local chromatin structure, or in trans via transcripts derived from the repeats(2-4). Here we show that a satellite repeat in the mosquito Aedes aegypti promotes sequence-specific gene silencing via the expression of two PIWI-interacting RNAs (piRNAs). Whereas satellite repeats and piRNA sequences generally evolve extremely quickly(5-7), this locus was conserved for approximately 200 million years, suggesting that it has a central function in mosquito biology. piRNA production commenced shortly after egg laying, and inactivation of the more abundant piRNA resulted in failure to degrade maternally deposited transcripts in the zygote and developmental arrest. Our results reveal a mechanism by which satellite repeats regulate global gene expression in trans via piRNA-mediated gene silencing that is essential for embryonic development.

A conserved satellite repeat in the mosquito Aedes aegypti encodes PIWI-interacting RNAs that promote sequence-specific gene silencing in trans and have an essential role in embryonic development.

Levels of gene expression underpin organismal phenotypes(1,2), but the nature of selection that acts on gene expression and its role in adaptive evolution remain unknown(1,2). Here we assayed gene expression in rice (Oryza sativa)(3), and used phenotypic selection analysis to estimate the type and strength of selection on the levels of more than 15,000 transcripts(4,5). Variation in most transcripts appears (nearly) neutral or under very weak stabilizing selection in wet paddy conditions (with median standardized selection differentials near zero), but selection is stronger under drought conditions. Overall, more transcripts are conditionally neutral (2.83%) than are antagonistically pleiotropic(6) (0.04%), and transcripts that display lower levels of expression and stochastic noise(7-9) and higher levels of plasticity(9) are under stronger selection. Selection strength was further weakly negatively associated with levels of cis-regulation and network connectivity(9). Our multivariate analysis suggests that selection acts on the expression of photosynthesis genes(4,5), but that the efficacy of selection is genetically constrained under drought conditions(10). Drought selected for earlier flowering(11,12) and a higher expression of OsMADS18 (Os07g0605200), which encodes a MADS-box transcription factor and is a known regulator of early flowering(13)-marking this gene as a drought-escape gene(11,12). The ability to estimate selection strengths provides insights into how selection can shape molecular traits at the core of gene action.

Phenotypic selection analysis is used to estimate the type and strength of selection that acts on more than 15,000 transcripts in rice (Oryza sativa), which provides insight into the adaptive evolutionary role of selection on gene expression.