An ATAC-seq atlas of chromatin accessibility in mouse tissues

Abstract

17The Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) is a 18 fundamental epigenomics approach and has been widely used in profiling the chromatin 19 accessibility dynamics in multiple species. A comprehensive reference of ATAC-seq datasets 20 for mammalian tissues is important for the understanding of regulatory specificity and 21 developmental abnormality caused by genetic or environmental alterations. Here, we report 22 an adult mouse ATAC-seq atlas by producing a total of 66 ATAC-seq profiles from 20 primary 23 tissues of both male and female mice. The ATAC-seq read enrichment, fragment size 24 distribution, and reproducibility between replicates demonstrated the high quality of the full 25 dataset. We identified a total of 296,574 accessible elements, of which 26,916 showed tissue-26 specific accessibility. Further, we identified key transcription factors specific to distinct tissues 27 and found that the enrichment of each motif reflects the developmental similarities across 28 tissues. In summary, our study provides an important resource on the mouse epigenome and 29 2 will be of great importance to various scientific disciplines such as development, cell 30 reprogramming, and genetic disease. 32Background & Summary 33Although most of the protein-coding genes in human and model animals such as mouse have 34 been extensively annotated, vast regions of the genome are noncoding sequences (e.g., 35roughly 98% of the human genome) and still poorly understood 1,2 . During the last decade, the 36 development of next-generation sequencing (NGS) based epigenomics techniques (e.g., ChIP-37 seq and DNase-seq) have significantly facilitated the identification of functional genomic 38 regions 3 . For example, by comparing the histone modifications and transcription factor (TF) 39 binding patterns throughout the mouse genome in a wide spectrum of tissues and cell types, 40 Yue et al. 4,5 have made significant progress towards a comprehensive catalog of potential 41 functional elements in the mouse genome. So far, the international human epigenome 42 consortium (IHEC), including ENCODE and the NIH Roadmap epigenomics projects, have 43 profiled thousands of epigenomes including DNA methylation, genome-wide binding of TFs, 44 histone modifications, and chromatin accessibility. This has resulted in the discovery of over 45 5 million cis-regulatory elements (CREs) in the human genome 6-8 . These data resources have 46 created an important baseline for further study of diverse biological processes, such as 47 development, cell reprogramming, and human disease 9-13 . 48 49 The accessibility of CREs, which is important for switching on and off gene expression 14 , 50 is strongly associated with transcriptional activity. To date, detection of DNase I hypersensitive 51 sites (DHSs) within chromatin by DNase-seq has been extensively used to map accessible 52 genomic regions in diverse organisms including the laboratory mouse 5 . In 2013, Buenrostro et 53 al. 15 reported an alternative approach, termed ATAC...