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Cell-type specific epigenetic regulome in Systemic Sclerosis skin

ABSTRACT: Skin systemic sclerosis (Scleroderma, SSc) is an autoimmune disease while its epigenetic regulatory mechanism is not known. We surveyed the genome-wide active regulatory elements in fresh human skin cells, using Assay of Transposase Accessible Chromatin with sequencing (ATAC-seq) in longitudinal skin from healthy volunteers and affected and unaffected skin from patients with SSc. We created robust pipelines that enable accurate single molecule counting and allelic discrimination from clinical material in vivo without clonal expansion. We generated high-resolution epigenetic regulomes of 9 cell types in normal and SSc skins, and identified 106044 cell type specific accessible sites. Motif analysis of these peaks predicted known and novel transcription factors regulating each cell type. For each cell type, we discovered thousands of accessible sites are differential in normal versus unaffected and affected skin from patients with SSc. We predicted novel transcription factors regulating SSc in a cell type specific manner, and predicted the relative contributions of each cell type in driving skin SSc. ATAC-seq also revealed novel elements that escape X chromosome inactivation, which coordinately impact genes with immune function.

ORGANISM(S): Homo sapiens

PROVIDER: GSE99702 | GEO | 2020/10/20

REPOSITORIES: GEO

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