The Chromatin Accessibility Landscape of Adult Rat

The use of animalmodels has greatly facilitated biomedical discoveries to better understand human physiology and diseases (Baldini, 2010). For example, mice are widely used in biomedical research with advantages in fast breeding, easy feeding, and genetic engineering (Gurumurthy et al., 2020). Multi-omics datasets in mouse models [e.g., RNA-seq (Koh et al., 2016; Söllner et al., 2017; Han et al., 2018), ChIP-seq (Dahl et al., 2016; Liu et al., 2016; Zhang et al., 2016), and ATAC-seq (Assay for Transposase-Accessible Chromatin coupled with next-generation sequencing) (Wu et al., 2016; Cusanovich et al., 2018a; Liu et al., 2019)] are largely accumulating, at either tissue or single-cell levels, in both developmental (Dahl et al., 2016; Liu et al., 2016; Wu et al., 2016; Zhang et al., 2016) and pathological (Park et al., 2018) studies, further advancing our understanding of complex diseases. In contrast, while the Norway rat allows more precise modeling of complex human disorders [such as cardiovascular and psychiatric disease (Abbott, 2009; Jacob, 2010)], very few multi-omics studies have been performed on this model since the completion of the full genome sequencing of Brown Norway (BN) rat strain in 2004 (Gibbs and Pachter, 2004). In 2017, Söllner et al. (2017) were the first to conduct a comprehensive tissue-level transcriptome study on 13 tissues of rat and mouse tissues and found that, while the majority of genes are highly conserved, there are also few hundreds of genes that displayed opposite expression patterns in rats and mice. Hence, additional transcriptome and chromatin openness profilings would be of great importance to further unravel regulatory complexities of the rat genome. In neuroscience, social behaviors such as grooming, sniffing, and chasing and their relationships with disease phenotypes have been assessed in great details in rat models (Meaney and Stewart, 1981; Schweinfurth, 2020). For example, a recent study has focused on both proteomic and transcriptomic profiling of the rat amygdala following a social play experiment and reported that the GABAergic, glutamatergic, and G-protein–coupled receptor signaling can be altered by social contexts (Alugubelly et al., 2019). By using rat as a model, future studies along this line would further illustrate mechanistic relationship between brain regions and social play behaviors. Comprehensive omics datasets have paved the way for important discoveries in physiology, diseases, social behaviors, and many other areas. In this regard, previous studies have generated a collection of omics references (including genome, transcriptome, epigenome, and proteome) for model organisms such as human (Collins et al., 2003; Cao et al., 2020; Domcke et al., 2020), mouse (Cusanovich et al., 2018a; Han et al., 2018), worm (Gerstein et al., 2010; Li et al., 2014; Daugherty et al., 2017), and fly (Adams et al., 2000; Graveley et al., 2011; Cusanovich et al., 2018b). However, rat multi-omics data resources are still lacking. In this study, we comprehensively profiled the chromatin accessibility of 10 body organs (pancreas, adrenal gland, spleen, ovary, heart, ileum, lung, kidney, liver, thymus) and 12 different brain regions in female andmale rats (somatosensory cortex, motor cortex, primary visual cortex, auditory cortex, prefrontal cortex, thalamus, cerebellum, striatum, hypothalamus, amygdala, hippocampus, olfactory bulb), by applying ATACseq (Buenrostro et al., 2013, 2015; Corces et al., 2017). This approach led to the identification of 397,691 chromatin accessible elements, with 34,219 body organ–specific peaks and 38,502 brain-specific peaks that were further characterized as tissuespecific regulatory elements. Interestingly, many of the enriched tissue-specific transcription factors were validated by previous studies (Liu et al., 2019). Here we provide a comprehensive rat tissue–specific chromatin accessibility landscape that would serve as an invaluable resource for future rat-related studies.