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Knowledge of locations and activities ofcis-regulatory elements (CREs) is needed to decipher basic mechanisms of gene regulation and to understand the impact of genetic variants on complex traits. Previous studies identified candidate CREs (cCREs) using epigenetic features in one species, making comparisons difficult between species. In contrast, we conducted an interspecies study defining epigenetic states and identifying cCREs in blood cell types to generate regulatory maps that are comparable between species, using integrative modeling of eight epigenetic features jointly in human and mouse in our Validated Systematic Integration (VISION) Project. The resulting catalogs of cCREs are useful resources for further studies of gene regulation in blood cells, indicated by high overlap with known functional elements and strong enrichment for human genetic variants associated with blood cell phenotypes. The contribution of each epigenetic state in cCREs to gene regulation, inferred from a multivariate regression, was used to estimate epigenetic state regulatory potential (esRP) scores for each cCRE in each cell type, which were used to categorize dynamic changes in cCREs. Groups of cCREs displaying similar patterns of regulatory activity in human and mouse cell types, obtained by joint clustering on esRP scores, harbor distinctive transcription factor binding motifs that are similar between species. An interspecies comparison of cCREs revealed both conserved and species-specific patterns of epigenetic evolution. Finally, we show that comparisons of the epigenetic landscape between species can reveal elements with similar roles in regulation, even in the absence of genomic sequence alignment. 

Abstract Multiple recent observations in the mesosphere have revealed large-scale Kelvin–Helmholtz instabilities (KHI) exhibiting diverse spatial features and temporal evolutions. The first event reported by Hecht et al. exhibited multiple features resembling those seen to arise in early laboratory shear-flow studies described as “tube” and “knot” (T&K) dynamics by Thorpe. The potential importance of T&K dynamics in the atmosphere, and in the oceans and other stratified and sheared fluids, is due to their accelerated turbulence transitions and elevated energy dissipation rates relative to KHI turbulence transitions occurring in their absence. Motivated by these studies, we survey recent observational evidence of multiscale Kelvin–Helmholtz instabilities throughout the atmosphere, many features of which closely resemble T&K dynamics observed in the laboratory and idealized initial modeling. These efforts will guide further modeling assessing the potential importance of these T&K dynamics in turbulence generation, energy dissipation, and mixing throughout the atmosphere and other fluids. We expect these dynamics to have implications for parameterizing mixing and transport in stratified shear flows in the atmosphere and oceans that have not been considered to date. Companion papers describe results of a multiscale gravity wave direct numerical simulation (DNS) that serendipitously exhibits a number of KHI T&K events and an idealized multiscale DNS of KHI T&K dynamics without gravity wave influences. Significance StatementKelvin–Helmholtz instabilities (KHI) occur throughout the atmosphere and induce turbulence and mixing that need to be represented in weather prediction and other models of the atmosphere and oceans. This paper documents recent atmospheric evidence for widespread, more intense, features of KHI dynamics that arise where KH billows are initially discontinuous, misaligned, or varying along their axes. These features initiate strong local vortex interactions described as “tubes” and “knots” in early laboratory experiments, suggested by, but not recognized in, earlier atmospheric and oceanic profiling, and only recently confirmed in newer, high-resolution atmospheric imaging and idealized modeling to date.