Integrative analysis of haplotype-resolved epigenomes across human tissues

Abstract

As part of the Epigenome Roadmap project, this study uses a chromosome-spanning haplotype reconstruction strategy to construct haplotype-resolved epigenomic maps for a diverse set of human tissues; the maps reveal extensive allelic biases in chromatin state and transcription, which vary across individuals due to genetic backgrounds. As part of the Epigenome Roadmap project, Bing Ren and colleagues use a chromosome-spanning haplotype reconstruction strategy to construct haplotype-resolved epigenomic maps for a diverse set of human tissues. The maps reveal extensive allelic biases in chromatin state and transcription, which vary across tissues and between individuals. They authors investigate cis-regulatory relationships between genes and their control sequences and tissue-restricted activities of repetitive elements. Allelic differences between the two homologous chromosomes can affect the propensity of inheritance in humans; however, the extent of such differences in the human genome has yet to be fully explored. Here we delineate allelic chromatin modifications and transcriptomes among a broad set of human tissues, enabled by a chromosome-spanning haplotype reconstruction strategy1. The resulting large collection of haplotype-resolved epigenomic maps reveals extensive allelic biases in both chromatin state and transcription, which show considerable variation across tissues and between individuals, and allow us to investigate cis-regulatory relationships between genes and their control sequences. Analyses of histone modification maps also uncover intriguing characteristics of cis-regulatory elements and tissue-restricted activities of repetitive elements. The rich data sets described here will enhance our understanding of the mechanisms by which cis-regulatory elements control gene expression programs.