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Allele-specific chromatin accessibility in early adolescence mouse liver resolved on a Collaborative Cross graph pangenome

ABSTRACT: To investigate the functional and adaptive significance of allele-specific candidate cis-regulatory elements (cCREs), we generated ATAC-seq on liver tissue from two 25-day-old F1 hybrid mice, bred from a CC032 mother and a CC072 father. Reads were mapped to the Collaborative Cross pangenome graph and phased into CC032 and CC072 alleles. Because no peak caller currently works directly on minigraph-cactus graphs, reads were surjected to GRCm38 for peak calling with MACS2. Counting phased reads on both alleles at 102,412 reproducible cCREs and testing for differential accessibility identified 1,805 allele-specific cCREs (1.7%) between the maternal and paternal genomes. About 72% of these carry SNVs and/or SVs from one allele, and they are enriched in promoters, introns and intergenic regions as well as in SINE, LINE and LTR transposable-element subfamilies.

ORGANISM(S): Mus musculus

PROVIDER: GSE345488 | GEO | 2026/08/31

REPOSITORIES: GEO

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Project description:Probing epigenetic features on long molecules of DNA has tremendous potential to advance our understanding of the phased epigenome. In this study, we evaluate CpG methylation and chromatin accessibility simultaneously on long strands of DNA using GpC methyltransferase to exogenously label open chromatin, coupled with nanopore sequencing technology. We performed nanopore sequencing of Nucleosome Occupancy and Methylome (nanoNOMe) on four human cell lines (GM12878, MCF-10A, MCF-7, MDA-MB-231), and demonstrate the ability to directly measure methylation and chromatin accessibility in genomic features such as structural variations and repetitive elements. The long single-molecule resolution allows footprinting of protein and nucleosome binding and determining the combinatorial promoter epigenetic state on individual molecules. Long-read sequencing makes it possible to robustly assign reads to haplotypes, enabling allele-specific epigenetic analysis across the genome. We use existing SNV data on GM12878 to present the first fully phased human Probing epigenetic features on long molecules of DNA has tremendous potential to advance our understanding of the phased epigenome. We evaluate CpG methylation and chromatin accessibility simultaneously on long strands of DNA using GpC methyltransferase to exogenously label open chromatin, coupled with nanopore sequencing technology. We performed nanopore sequencing of Nucleosome Occupancy and Methylome (nanoNOMe) on four human cell lines (GM12878, MCF-10A, MCF-7, MDA-MB-231), and demonstrate the ability to directly measure methylation and chromatin accessibility in genomic features such as structural variations and repetitive elements. The long single-molecule resolution allows footprinting of protein and nucleosome binding and determining the combinatorial promoter epigenetic state on individual molecules. Long-read sequencing makes it possible to robustly assign reads to haplotypes, enabling allele-specific epigenetic analysis across the genome. We use existing SNV data on GM12878 to present the first fully phased human epigenome, consisting of chromosome-level allele-specific profiles of CpG methylation and chromatin accessibility.mosome-level allele-specific profiles of CpG methylation and chromatin accessibility.

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Allele-specific chromatin accessibility in early adolescence mouse liver resolved on a Collaborative Cross graph pangenome

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